Professional Documents
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Introduction
Over the last 25 years, great efforts have been made to develop techniques to assess respiratory muscle function. Research output in this area has progressively increased, with the
number of peer reviewed articles published on respiratory muscle function having increased remarkably during the 19952000
period compared with 19801985.
This official joint statement represents the work of an expert ATS/ERS committee, which reviewed the merits of currently known techniques available to evaluate respiratory muscle function. The statement consists of 10 sections, each addressing
a major aspect of muscle function or a particular field of application. Each section addresses the rationale for the techniques,
their scientific basis, the equipment required, and, when pertinent, provides values obtained in healthy subjects or in patients. Some of the techniques reviewed in this statement have
thus far been used primarily in clinical research and their full
potential has not yet been established; however, they are mentioned for the purpose of stimulating their further development.
Through continued efforts in the area of respiratory muscle
testing, it is anticipated that there will be further enhancement
of diagnostic and treatment capabilities in specialties such as
intensive care, sleep medicine, pediatrics, neurology, rehabilitation, sports medicine, speech therapy, and respiratory
medicine.
The most frequently noted abnormality of lung volumes in patients with respiratory muscle weakness is a reduction in vital
capacity (VC). The pattern of abnormality of other subdivisions of lung volume is less consistent. Residual volume (RV)
is usually normal or increased, the latter particularly with
marked expiratory weakness (1). Consequently, total lung capacity (TLC) is less markedly reduced than VC, and the RV/
TLC and FRC/TLC ratios are often increased without necessarily implying airway obstruction.
The VC is limited by weakness of both the inspiratory muscles, preventing full inflation, and expiratory muscles, inhibiting full expiration. In addition to the direct effect of loss of
muscle force, reductions in compliance of both the lungs (2)
and chest wall (3) also contribute to the reduction of VC in patients with chronic respiratory muscle weakness. In severe
weakness, the TLC and VC relate more closely to lung compliance than to the distending force (4, 5) (Figure 1). The
mechanism of reduced lung compliance is unclear. Contrary to
earlier suggestions, it is probably not simply due to widespread microatelectasis (6). Static lung volumes may also be
affected in some patients by coexistent lung or airway disease.
Vital capacity, thus, reflects the combined effect of weakness
and the static mechanical load on the respiratory muscles.
In mild respiratory muscle weakness, VC is less sensitive
than maximum respiratory pressures. However, the curvilinear relation between VC and maximum inspiratory pressure
(5) (Figure 2) implies that, in more advanced disease, marked
reductions in VC can occur with relatively small changes in
maximum pressures.
In patients with isolated or disproportionate bilateral diaphragmatic weakness or paralysis, the VC shows a marked fall
in the supine compared with the erect posture because of the
action of gravitational forces on the abdominal contents. In
some patients, this postural fall may exceed 50%. In most normal subjects, VC in the supine position is 510% less than
when upright (7) and a fall of 30% or more is generally associated with severe diaphragmatic weakness (8).
Disadvantages
Advantages
VC has excellent standardization, high reproducibility and wellestablished reference values. It is easily performed, widely available, and economical. It is quite sensitive for assessing progress
in moderate to severe respiratory muscle weakness. The rate of
decline has been shown to predict survival in both amyotrophic
lateral sclerosis (11) and Duchenne muscular dystrophy (12).
Recommendations and requirements for maximum flowvolume curves are covered in detail elsewhere (9, 10).
Advantages
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Disadvantages
Intersubject
variability is greater than for VC. Reference val
ues for VEmax at standard percentages of FVC may present
problems of interpretation.
Applications
Figure 3. Schematic maximum expiratory and inspiratory flowvolume curves in a patient with severe respiratory muscle weakness (solid
line) compared with predicted (dotted line). Volume is expressed in absolute
terms (i.e., percent predicted).
Note marked reductions in FVC,
VEmax at higher volumes, and VImax at all volumes. Note also the
blunted
contour of the expiratory curve and the abrupt cessation of
Applications
Advantages
523
Methodology
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If phasic contraction of scalenes, sternocleidomastoids, pectoral muscles, or abdominal muscles can be palpated, it is safe to
conclude that respiratory motor output is above normal.
When respiratory muscles are chronically severely weak
and arterial PCO2 begins to rise, two explanations are possible.
The muscles may be so weak that they cannot continually generate sufficient alveolar ventilation. Otherwise, an abnormality of the ventilatory control system may be allowing the PCO2
to rise even though the muscles themselves are quite capable
of keeping it normal. A gradual shift in the PCO2 set point of
the controller does seem to occur in some patients with muscle
disease, as it does in some cases of sleep apnea and chronic
obstructive pulmonary disease.
Laboratory tests of overall respiration that have been used
to try to assess the control system include inhalation of hypercapnic or hypoxic gas mixtures to stimulate chemoreceptors,
with measurements of ventilation or occlusion pressure to assess motor output, and sleep studies to monitor behavior of
the control system during sleep.
In patients with weak muscles, interpretation of slopes of
conventional ventilatory curves is clouded for several reasons.
The output of the controller is abnormally high when ventilation is normal. The controller may therefore be on the
nonlinear part of its normal response curve.
The high motor neuron output cannot be measured directly
and its mechanical effect (e.g., ventilation) is reduced in the
presence of weakness.
The response will become flat if ventilation nears the limit of
respiratory muscle endurance and that limit may be only a
short distance above resting ventilation.
Abnormal central control of respiration is well documented
in bulbar poliomyelitis and other conditions affecting the central nervous system, presumably because of direct involvement of medullary respiratory centers. It has been suggested
that certain muscle diseases are also associated with primary
abnormalities of central respiratory control; these conditions
include myotonic dystrophy, acid maltase deficiency, and other
congenital myopathies. Impaired ventilatory responses to CO2
and/or hypoxia have frequently been described, but in many
cases, respiratory muscle function was assessed inadequately.
In myotonic dystrophy it has been shown that the relations between hypercapnia and both maximum respiratory pressures
and VC are similar to those in nonmyotonic diseases (30).
Occlusion pressure is the pressure generated in the airway
(and by inference the pressure generated in the pleural space)
by contraction of inspiratory muscles when the airway has
been occluded at end expiration. It was introduced to separate
hypoventilation due to high pulmonary resistance or elastance
from hypoventilation due to a failure of the respiratory pump
apparatus (i.e., the muscles, passive components of the chest
wall, and the control system) (31, 32). Occlusion pressure amplitude does not directly assess either the degree of muscle
weakness or the degree of neuronal adjustment to the weakness. P0.1 is the pressure generated in the first 100 milliseconds
of inspiration against an occluded airway. Its timing is such
that it is not influenced by the conscious response to occlusion
and as an index of ventilatory drive it has the advantage over
ventilation of being independent of the mechanical properties
of the lung (31). It is, however, dependent on the contractile
state and function of the respiratory muscles and consequently
on the lung volume at which it is measured. For example, because of the lengthtension relationship of the muscles, a reduced value for a given neural output would be expected with
pulmonary hyperinflation and an elevated FRC. On the other
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For assessment of ventilatory responses to hypercapnia or hypoxia (36), the subject inhales a gas mixture that causes a
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reduced. Reduction is due to inability to achieve full distension of the lungs at TLC and consequent failure to expose all
the alveolar surface to carbon monoxide. As with other extrapulmonary causes of lung volume restriction, the transfer coefficient (KCO) is often supernormal.
Advantages
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airway muscles are weak and also in patients with extrapyramidal disorders (e.g., Parkinsons disease).
8. PaO2 and PaCO2 are affected by muscle weakness. Mild weakness causes slight hypoxemia and hypocapnia; severe weakness causes hypercapnia, but only when strength is 40%
predicted. A raised bicarbonate level may suggest muscle
weakness.
9. Respiratory muscle weakness may cause desaturation and
hypercapnia during REM sleep.
10. CO transfer (DLCO) in patients with muscle weakness is
normal or mildly reduced but, as with other causes of extrapulmonary lung volume restriction, the transfer coefficient (KCO) is often raised.
Clinical Applications
References
1. Kreitzer SM, Saunders NA, Tyler HR, Ingram RH. Respiratory muscle function in amyotrophic lateral sclerosis. Am Rev Respir Dis 1978;117: 437447.
2. Gibson GJ, Pride NB, Newsom Davis J, Loh C. Pulmonary mechanics in
patients with respiratory muscle weakness. Am Rev Respir Dis 1977;
115:389395.
3. Estenne M, Heilporn A, Delhez L, Yernault J-C, De Troyer A. Chest
wall stiffness in patients with chronic respiratory muscle weakness.
Am Rev Respir Dis 1983;128:10021007.
4. Gibson GJ, Pride NB. Lung mechanics in diaphragmatic paralysis. Am
Rev Respir Dis 1979;119:119120.
5. De Troyer A, Borenstein S, Cordier R. Analysis of lung volume restriction
in patients with respiratory muscle weakness. Thorax 1980;35:603610.
6. Estenne M, Gevenois PA, Kinnear W, Soudon P, Heilporn A, De
Troyer A. Lung volume restriction in patients with chronic respiratory
muscle weakness: the role of microatelectasis. Thorax 1993;48:698701.
7. Allen SM, Hunt B, Green M. Fall in vital capacity with weakness. Br J
Dis Chest 1985;79:267271.
8. Laroche CM, Carroll N, Moxham J, Green M. Clinical significance of severe isolated diaphragm weakness. Am Rev Respir Dis 1988;138:862866.
9. Quanjer PH. Standardised lung function testing. Eur Respir J 1993;
6(Suppl 16):3S102S.
10. American Thoracic Society. Standardisation of spirometry: 1987 update.
Am Rev Respir Dis 1987;136:12851298.
11. Fallat RJ, Jewitt B, Bass M, Kamm B, Norris FH. Spirometry in amyotrophic lateral sclerosis. Arch Neurol 1979;36:7480.
12. Phillips M, Smith PEM, Carroll N, Edwards RHT, Calverley PMA.
Does nocturnal oxygen desaturation predict survival in childhood onset muscular dystrophy? Thorax 1997;52:A18.
13. Black LF, Hyatt RE. Maximal static respiratory pressures in generalised
neuromuscular disease. Am Rev Respir Dis 1971;103:641650.
14. Wesseling G, Quaedvlieg FCM, Wouters EFM. Oscillatory mechanics of the
respiratory system in neuromuscular disease. Chest 1992;102:17521757.
15. Polkey MI, Lyall RA, Green M, Leigh PN, Moxham J. Expiratory muscle function in amyotrophic lateral sclerosis. Am J Respir Crit Care
Med 1998;158:734741.
16. Estenne M, van Muylem A, Gorini M, Kinnear W, Heilporn A, de
Troyer A. Effects of abdominal strapping on forced expiration in tetraplegic patients. Am J Respir Crit Care Med 1998;157:9598.
17. Vincken WG, Cosio MG. Flow oscillations on the flowvolume loop:
clinical and physiological implications. Eur Respir J 1989;2:543549.
18. Serisier DE, Mastaglia FL, Gibson GJ. Respiratory muscle function and
ventilatory control. I. In patients with motor neurone disease; II. In
patients with myotonic dystrophy. Q J Med 1982;51:205226.
19. Braun NMT, Arora NS, Rochester DF. Respiratory muscle and pulmonary function in polymyositis and other proximal myopathies. Thorax
1983;38:616623.
20. Tzelepis GE, McCool FD, Friedman JH, Hoppin FG. Respiratory muscle dysfunction in Parkinsons disease. Am Rev Respir Dis 1988;138:
266271.
21. Lane DJ, Hazleman B, Nichols PJR. Late onset respiratory failure in patients with previous poliomyelitis. Q J Med 1974;43:551568.
22. Harrison BDW, Collins JV, Brown KGE, Clark TJH. Respiratory failure in neuromuscular diseases. Thorax 1971;26:579584.
23. Bye PTP, Ellis ER, Issa FG, Donnelly PM, Sullivan CE. Respiratory
failure and sleep in neuromuscular disease. Thorax 1990;45:241247.
24. White JES, Drinnan MJ, Smithson AJ, Griffiths CJ, Gibson GJ. Respiratory muscle activity and oxygenation during sleep in patients with
muscle weakness. Eur Respir J 1995;8:807814.
EXERCISE TESTING
In many patients with muscle weakness, exercise is limited,
and therefore, maximum oxygen consumption is reduced because of weakness of the leg muscles rather than cardiorespiratory factors. The limited available data suggest that the relation of workload to oxygen consumption is normal, as also are
indices of submaximal exercise performance (42).
Advantages
Formal testing allows confirmation and quantification of exercise incapacity and may aid elucidation of its mechanism.
Disadvantages
Exercise testing may help determine the main factor(s) limiting exercise capacity, especially if related or coexistent cardiac
or pulmonary disease is present or suspected.
CONCLUSION
This Section of the Statement has explored the usefulness of
analyzing the results of pulmonary function tests to infer alterations in respiratory muscle function. Some such inferences
are as follows:
1. Respiratory muscle weakness reduces VC.
2. Expiratory muscle weakness can increase RV.
3. Reduction in chest wall and lung compliance, as a consequence
of muscle weakness, reduces lung volumes, notably VC.
4. A fall in VC in the supine position, compared with when
upright, suggests severe diaphragm weakness or paralysis.
5. With respiratory muscle weakness the maximal expiratory
and inspiratory flowvolume loops show a reduction in effort-dependent flows (peak flows) and a sharp fall in endexpiratory flow.
6. Reduced maximal flows in neuromuscular disease may reflect poor respiratory muscle coordination.
7. Maximum inspiratory and expiratory flowvolume curves
showing sawtooth oscillations are seen when the upper
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34.
35.
36.
37.
38.
39.
40.
41.
42.
important indicator for successful weaning in patients with chronic obstructive pulmonary disease. Am Rev Respir Dis 1987;135:107113.
Baydur A. Respiratory muscle strength and control of ventilation in patients with neuromuscular disease. Chest 1991;99:330338.
Holle RHO, Schoene RB, Pavlin EJ. Effect of respiratory muscle weakness
on P0.1 induced by partial curarization. J Appl Physiol 1984;57: 11501157.
Cherniack NS, Dempsey J, Fencl V, Fitzgerald RS, Lourenco RV, Rebuck AS, Rigg J, Severinghaus JW, Weil JW, Whitelaw WA, et al.
Workshop on assessment of respiratory control in humans. I. Methods
of measurement of ventilatory responses to hypoxia and hypercapnia.
Am Rev Respir Dis 1977;115:177181.
Read DJC. A clinical method for assessing the ventilatory response to
CO2. Australas Ann Med 1967;16:20.
Rebuck AS, Campbell EJM. A clinical method for assessing the ventilatory response to hypoxia. Am Rev Respir Dis 1974;109:345.
Weil JW, Byrne-Quinn E, Sodal JE, Filey GF, Grover RF. Acquired attenuation of chemoreceptor function in chronically hypoxic man at altitude. J Clin Invest 1971;50:186.
Cunningham DJC, Cormack RS, ORiordan JLH, Jukes MGM, Lloyd
BB. An arrangement for studying the respiratory effects in man of
various factors. Q J Exp Physiol 1957;42:294.
Whitelaw WA, Derenne J-P. Airway occlusion pressure. J Appl Physiol
1995;74:14751483.
Carroll JE, Hagberg JM, Brooks MH, Shumate JB. Bicycle ergometry
and gas exchange measurements in neuromuscular disease. Arch Neurol 1979;36:457461.
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For the measurement of Pes, good results have been provided by latex balloons 510 cm long, 3.55 cm in perimeter, and
with a thin wall (8, 13, 14). For accurate transmission of pressure, air should be introduced into the balloon until it is fully
distended to smooth out folds, and then most of the air removed
so that a volume is retained at which the rubber is unstretched
without distending the esophagus significantly. A volume of 0.5
ml is adequate for balloons with these characteristics. The volume displacement coefficient of the balloon cathetertransducer system should be measured, particularly if the balloon will
measure positive pressures, to ensure that the pressure level to
be measured does not completely empty the balloon into the
catheter and transducer. Thus, if high positive pressures are to
be measured (e.g., for Pes during maximal expiratory maneuvers) a volume of 0.5 ml may be inadequate (6). Balloon volumes should be checked repeatedly during measurements.
For the measurement of Pga, balloon volume is less crucial
and measurements can be made with a balloon volume of 12
ml, given that this remains within the range of volume over
which the rubber is unstretched. If studies of relatively long
duration are planned, the walls of the gastric balloon should
be thicker than those of esophageal balloons to increase resilience to gastric secretions.
Respiratory muscle studies can involve dynamic maneuvers
with high rates of change in pressure (e.g., sniffs and twitches)
resulting in a significant risk of a damped signal if the frequency response of the measuring system is inadequate, as may
occur if the internal diameter of the catheter is too small or
the gas volume too large. Polyethylene catheters with an internal diameter 1.41.7 mm and 70100 cm in length provide,
when associated with adequate transducers, an appropriate
frequency response (6).
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Scientific basis. Measurement of the maximum static inspiratory pressure that a subject can generate at the mouth (PImax)
or the maximum static expiratory pressure (PEmax) is a simple
way to gauge inspiratory and expiratory muscle strength. The
pressure measured during these maneuvers reflects the pressure developed by the respiratory muscles (Pmus), plus the
passive elastic recoil pressure of the respiratory system including the lung and chest wall (Prs) (Figure 2 [33]). At FRC, Prs
is zero so that Pmo represents Pmus. However, at residual volume (RV), where PImax is usually measured, Prs may be as
much as 30 cm H2O, and thus makes a significant contribution to PImax of up to 30% (or more if Pmus is decreased).
Similarly, PEmax is measured at total lung capacity (TLC),
where Prs can be up to 40 cm H2O. Clinical measures and
normal values of PImax and PEmax do not conventionally subtract the respiratory system recoil.
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PEmax
PImax
Source (Ref.)
Mouthpiece Design
23.4 4.5
22.8 4.1
21.2 4.4
15.1 8.0
14.4 3.3
13.7 3.7
12.7 3.1
12.1 2.1
12.4 2.7
11.1 3.5
10.4 3.0
10.3 2.5
40
26
41
42
43
44
Tube
Tube
Tube
Flanged
Flanged
Flanged
16.1 2.9
14.9 2.6
13.5 6.7
9.2 3.2
9.1 1.6
8.7 2.3
9.6 2.4
8.5 1.5
8.9 2.4
7.0 2.6
7.2 2.1
6.9 2.3
40
26
41
42
43
44
Tube
Tube
Tube
Flanged
Flanged
Flanged
Male
106
60
80
325
80
46
Female
94
60
121
480
87
60
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loon catheter systems passed into the esophagus (see TECHNIQUES FOR PRESSURE MEASUREMENTS) to measure Pes as a reflection of Ppl or into the stomach where Pga can be used to
reflect Pab. Esophageal pressure does not include lung elastic
recoil pressure but does include chest wall recoil pressure. The
main indication for balloon catheter measurements of maximum respiratory muscle pressures is to estimate the strength
of the separate muscle groups, notably the diaphragm (from
Pdi), or to measure strength when the patient is unable to
maintain a proper seal around the mouthpiece.
With the balloon catheters in place, various maneuvers can
be used to assess global inspiratory muscle or diaphragm
strength. These tests are usually performed at FRC. In the
Mueller (maximal inspiratory) maneuver the diaphragm and
inspiratory muscles are contracted with the aim of creating the
biggest negative thoracic pressure without regard to abdominal
pressure. However, this usually does not generate maximum
Pdi (25, 52). As an alternative, the subject may perform an expulsive maneuver, wherein the individual is requested to bear
down as for defecation and simultaneously superimposes a
Mueller maneuver. When given visual feedback, this complex
maneuver can be mastered by trained subjects to give the largest values of Pdi (up to 240 cm H2O or more) (53). It may reflect nearly maximal neural activation of the diaphragm, perhaps with fiber lengthening (52, 54). However, the technique is
difficult for naive subjects and in the clinical setting (55).
Twitch occlusion studies have confirmed that such maneuvers
can produce maximal neural activation of the diaphragm (56).
Figure 5. (A) A typical pressure tracing from a subject performing a maximum expiratory maneuver (PEmax). A peak
pressure is seen and the 1-second average is determined
by calculating the shaded area. (B) A pressure tracing from
a subject performing a maximum inspiratory maneuver
(PImax).
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Men
Women
All
Pdi,sn
(cm H2O)
Mean
SD
Range
Mean
SD
Range
37
27
64
108
65
90
30
31
37
52164
1640
16164
148
121
137
24
25
28
112204
82182
82204
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Since 1980, PNS has been investigated as a technique for elucidating mechanical aspects of diaphragm function. The 1989
National Heart, Lung, and Blood Institute (NHLBI) workshop on respiratory muscle fatigue identified it as one of the
most promising techniques in this field (80).
The stimulus to the nerve, which can be an externally applied
electric field or secondary currents surrounding a magnetic field
(see MAGNETIC STIMULATION), elicits synchronized activation of
motor units and subsequent muscle contraction. The effects of
phrenic nerve stimulation can be studied both electrophysiologically (see STIMULATION TESTS in Section 3 of this Statement) and
mechanically (this Section).
Four main PNS techniques have been used, mostly in
healthy volunteers, less often in patients. Two of them, needle
stimulation (81, 82) and implanted wire stimulation (83), are
invasive, with the risk of hematoma and phrenic nerve damage. Needle stimulation is not now recommended, and is not
further discussed. Implanted wire stimulation is probably safer,
and may be a convenient means to obtain repeated twitches
over long periods of time. The two others techniques, transcutaneous electrical PNS (ES) and magnetic stimulation (MS),
have been more extensively studied and have minimal side effects.
Subjects in Phrenic Nerve Stimulation
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Figure 8. Pressures during a maximal voluntary cough in a normal subject showing high positive gastric pressures generated in abdomen
(Pga; thick line) and esophagus (Pes) with low Pdi during the maneuver.
pliant abdominal wall; this may be appropriate for physiological studies (56, 88, 89). In a clinical setting it is difficult to standardize a binding technique and so the abdomen is usually
unbound.
Transcutaneous Electrical Phrenic Nerve Stimulation
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Scientific basis. The ability of magnetic fields to stimulate nervous structures has long been known (93). Magnetic stimulation creates intense and brief magnetic fields, which, unlike
electric currents, are only mildly attenuated by natural barriers such as skin and bone. They can therefore reach deep nervous structures, where stimulation is produced in situ by the
electrical fields induced by the rapidly changing magnetic
fields (Figure 10). The mechanisms of neural response to magnetic stimulation are different from those of the response to
electrical stimulation (9497), and therefore the results obtained with the two techniques may have different interpretations. Nevertheless, magnetic stimulation has the advantage of
being relatively painless and is thus easily applicable in the
clinical setting. Several review articles were discussed by
Chokroverty (98).
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During the last 10 years, magnetic stimulation has been extensively used to stimulate the central nervous system in conscious humans (99). From the respiratory point of view, magnetic stimulation applied to the cervical spine (CMS) elicits a
bilateral diaphragm contraction (100). The coil is centered
over the spinous process of the seventh vertebral body (C7),
but this does not mean that the seventh roots are stimulated.
Depolarization of a nervous structure by magnetic stimulation
requires that the stimulating current and the nerve share a
common pathway: centering a circular 90-mm coil around C7
would, thus, generally stimulate the third to fifth cervical roots
(101103), depolarized in their intraforaminal segment (104,
105). Although it is generally believed that CMS provokes diaphragm contraction through the stimulation of cervical roots,
it has been suggested that the C7 CMS magnetic field may
reach the phrenic nerves anteriorly, through the neck, and
thus stimulate the phrenic nerve trunk at a point more distal
than with ES (106) (Figure 11).
Cervical magnetic stimulation also stimulates other elements of the cervical roots and nearby nerves, thus causing
some contraction of neck and upper rib cage muscles, as well
as diaphragm (100, 107109) (see COMPARISON BETWEEN TRANSCUTANEOUS ELECTRICAL PHRENIC NERVE STIMULATION AND CERVICAL MAGNETIC STIMULATION).
Methodology. The subject, comfortably seated in a chair, is
asked to bend the neck forward slightly. The coil is applied to
the back of the neck, its midline coinciding with the axis of the
vertebral column (Figure 11). Optimal results are generally
obtained with the coil centered around the spinous process of
the seventh cervical vertebra (C7), but slightly higher and
lower positions should be tried with monitoring of pressure or
EMG, although care may be required to obtain satisfactory
surface EMG signals. The optimal coil position may vary with
the size and neck morphology of the subject. Stimulation intensity is generally set to the maximal output of the stimulator
(see SUPRAMAXIMAL STIMULATION).
Several manufacturers provide magnetic stimulators suitable
for CMS. High-powered machines, capable of producing mag-
Focal magnetic phrenic nerve stimulation. Small figure of eightshaped magnetic coils can be used for focal stimulation (focal
MS) of the phrenic nerve in the neck unilaterally or bilaterally,
at the same point as stimulation by ES (114, 115). Bilateral focal
MS is easily applied by an operator standing in front of the sub-
538
ject and gives values for Pdi,tw and the Pga,tw/Pes,tw ratio that
are close to ES (115), thus avoiding any problems associated
with stimulating upper trunk muscles (see subsequent section).
This technique could make bilateral PNS easier in supine patients, as in the ICU, because for ES the operator has to stand
behind the patient and for CMS the subjects neck has to lie over
the coil, which may be uncomfortable and impede optimal positioning. Unilateral focal MS may allow assessment of the mechanical properties of one hemidiaphragm alone (87, 114, 116).
Anterior magnetic stimulation. The possibility of evoking a
bilateral diaphragm EMG response through anterior magnetic
stimulation (antMS) with a 90-mm circular coil similar to that used
for CMS, placed flat over the upper part of the sternum, has been
described (106). Anterior magnetic stimulation is potentially a
simple technique also applicable to supine subjects in difficult
settings, but pressure responses remain to be evaluated.
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Figure 12. Typical pressure tracings in response to phrenic nerve stimulation. Traces A to C show, respectively, the esophageal pressure
(Pes), gastric pressure (Pga), and transdiaphragmatic pressure (Pdi) responses to bilateral, supramaximal, electrical stimulation of the phrenic
nerve in the neck, in a patient with COPD (hence the relatively low
amplitudes). On the Pdi trace (C) are indicated some indexes often
used to describe quantitatively the twitch response: (1) Pdi,tw is the
amplitude of the response from baseline to peak; it is the result of the
interaction of diaphragm contraction with the rib cage and the abdomen; although not a direct measure of diaphragm intrinsic contractile
properties, it is related to diaphragm strength and can be used to
characterize it if all other intervening factors are otherwise kept identical (e.g., lung volume, thoracic geometry, rib cage and abdomen
compliance, diaphragm state of activation, etc.); (2) ttp and 1/2rt are
the time-to-peak and half-relaxation time, respectively; these indexes
are used to characterize the dynamics of diaphragm contraction, and
are influenced, for example, by muscle shortening or fatigue; and (3)
is the time constant of an exponential function fitted to the after-peak
decline in Pdi (often referred to as the relaxation time constant); it is
influenced by diaphragm intrinsic properties and, for example, is prolonged by fatigue. The trace in D illustrates the similarity in shape,
time dynamics, and amplitude in the Pes twitch (thin line) and the
mouth pressure (Pmo) twitch (thick line) to phrenic nerve stimulation,
in a normal healthy volunteer.
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to PNS (83, 84, 117, 119, 129134). This is a result of the inverse relationships of length with force in skeletal muscles,
and of lung volume with diaphragm length (36, 69, 125).
Pdi,tw decreases as lung volume increases, with a prominent
reduction in Pes,tw that is close to zero at TLC (83, 129131,
134136) (Figure 13). Isovolume changes in rib cage and abdominal configuration also influence Pdi,tw (83, 84, 125).
A long-standing increase in lung volume tends to be compensated for by adaptive mechanisms at the level of the sarcomere, known as length adaptation in animals (137141) and
probably in humans (131, 142). Thus, the observations made
during acute changes in lung volume may not be as relevant to
chronic hyperinflation.
How sensitive to changes in lung volume is the pressure response to PNS? Between FRC and TLC, Pdi,tw and Pmo,tw decrease by approximately 3%/100 ml (83, 84, 119, 130, 132), and
between RV and FRC by approximately 5%/100 ml (83, 128).
These changes appear to be reduced if care is taken to avoid potentiation (129) and may be less in the elderly (131, 134).
Lung volume, and if possible rib cage/abdominal configuration, should be carefully controlled when assessing PNS pressures in research settings. When PNS is repeated in patients
with labile lung volumes, FRC should be measured on the day
of the study. Assessing lung volume may be less crucial for
clinical assessment, recognizing that a change in Pdi,tw or
Pmo,tw can reflect changes in diaphragm properties, or lung
volume, or both.
Twitch potentiation. A transient increase in the contractility of a skeletal muscle follows its contraction. This phenomenon is called potentiation (143, 144).
The possibility of twitch potentiation should be taken into
account when interpreting studies involving PNS. A period of
quiet breathing, e.g., 15 min, should be allowed before recording diaphragm twitches, particularly if maximal maneuvers or
sniffs are performed beforehand (145147).
Hypertrophy of neck muscles. When there is a bilateral
paralysis, Pes,tw and Pdi,tw during ES are zero. With CMS,
coactivated neck muscles can, theoretically, produce some degree of Pes,tw during CMS. This effect may be small in most
subjects (148), but could be larger in patients with hypertrophied inspiratory neck muscles (149).
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(1)
Particular Techniques
541
The use of PNS-derived pressures to study the mechanical action of the diaphragm assumes that stimulation is bilateral and
supramaximal, and that care is taken to control for lung volume and twitch potentiation.
Research applications. Bilateral ES is an important tool in
human diaphragm research, used to study the properties of the
diaphragm and the mechanisms of its fatigue independently of
volitional influences. The twitch occlusion technique, as the
only means to separate the peripheral and central components
of diaphragm dysfunction, is also an important, if complex, research tool. The use of paired stimuli could facilitate research
on the frequency characteristics of diaphragm fatigue (174).
Cervical magnetic stimulation provides slightly different information from ES, mainly because of rib cage muscle coactivation. However, its simplicity for the subject and the operator makes it a valuable tool for clinical research, especially in
difficult settings, such as the ICU, or when repeated studies
are needed, such as the evaluation of therapeutic interventions.
Clinical applications. Contraindications. There are virtually no contraindications to ES and MS, but their use requires
some precautions. MS should not be performed in patients with a
cardiac pacemaker. Patients with orthopedic implants, even
metallic ones, can be studied with MS (e.g., candidates for
phrenic pacing after high cervical cord injury) (198) after sufficient time for consolidation.
Clinical use. Pressure responses to PNS play an important
part in the clinical evaluation of inspiratory muscle function.
Diaphragmatic weakness can be established and quantified with
PNS, particularly when voluntary maneuvers are equivocal. The
use of MS with Pmo may be an even simpler nonvolitional
measure.
The preoperative assessment of patients for possible phrenic
pacing after high cervical cord lesions constitutes a particular
application. PNS provides information on phrenic nerve con-
542
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2002
Pdi,tw
(cm H2O, mean)
Note
34.6
34.4
31.4
833
Mier (84)
Gandevia (155)
Mier (82)
24.4
28.0
19.429.3
Mador (90)
Wragg (107)
Eastwood (85)
28.9
29.7
2128
Laghi (108)
Similowski (109)
32.3
23.3
Similowski (131)
19.831.7
Needle stimulation
Implanted wire stimulation
15 control subjects referred for suspected diaphragm
weakness; significant overlap between groups; Pdi,tw was
discriminant only for diagnosis of severe diaphragm weakness
Supine position
3 subjects; comparison between transcutaneous electrical
stimulation and needle stimulation
Comparison CMSES
3 subjects; validation of a cervical apparatus aiming at
standardizing PNS for repeated studies: data reproducible
among 25 repeated studies
Comparison CMSES
Comparison CMSES
Mancini (182)
18.8
33.4
Wragg (107)
Wragg (146)
36.5
36.5
Laghi (184)
Hamnegard (129, 187)
Similowski (109)
Laghi (108)
38.9
1734
27.5
37.7
Comparison CMES
Comparison CMES
25.4
Patients with COPD
Similowski (131)
Wanke (183)
Polkey (134, 190)
1026
15.2
18.2
Bilateral ES
Bilateral ES
CMS
Definition of abbreviations: CMS cervical magnetic stimulation; COPD chronic obstructive pulmonary disease; ES electrical stimulation; Pdi,tw twitch transdiaphragmatic pressure; PNS phrenic nerve stimulation.
Values represent means or ranges.
duction time, which is important in making the decision to undertake pacing (198). It also provides an estimate of the degree of diaphragm disuse atrophy, which is an important
determinant of the reconditioning strategy (199).
Given that methodological precautions are rigorously respected, PNS is one of the more reproducible respiratory muscle tests, and this makes it suitable for follow-up studies (see
PHRENIC NERVE STIMULATION in Section 3 of this Statement).
used in humans to study the action of various abdominal muscles on the rib cage (200), and in a study of diaphragm maximal voluntary activation (155). From a therapeutic point of
view, its use has been considered to enhance cough in patients
with cervical cord injury (201). However, direct electrical stimulation is painful and supramaximality is difficult to achieve. It
is also difficult to activate all muscles groups at once.
Contraction of the abdominal muscles can also be provoked by stimulation of their parent nerves and roots (202).
Theoretically, this allows supramaximal stimulation (and therefore reproducibility) and, if the stimulus is widespread enough,
simultaneous activation of all abdominal muscles. Magnetic
stimulation over the vertebral column at the level of the eighth
to tenth thoracic vertebra could provide an easy-to-use nonvolitional assessment of abdominal muscle strength and fatigue
(202, 203).
CONCLUSION
The purpose of this Section is to describe the tests used to assess respiratory muscle strength. To test strength, pressures
543
544
26.
27.
28.
29.
30.
31.
32.
33.
34.
35.
36.
37.
38.
39.
40.
41.
42.
43.
44.
45.
46.
47.
48.
49.
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51.
52.
53.
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95.
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97.
98.
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107.
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112.
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115.
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APPENDIX: ABBREVIATIONS
Measures
P
L
V
EMG
PMG
alv
ab
abw
ao
aw
bs
di
es, oes
g, ga
Alveolar
Abdomen
Abdominal wall
Airway opening
Airway
Body surface
Diaphragm, transdiaphragmatic
Esophageal
Gastric
ia
mo
mus
nas
np
ph
pl
rc
rs
w, cw
ant
post
E
I
Intercostal/accessory muscles
Mouth
Muscle
Nostril, nasal
Nasopharynx
Phrenic
Pleural
Rib cage
Respiratory system (lung and chest wall)
Chest wall
Anterior
Posterior
Expiratory
Inspiratory
Maneuvers
co
max
sn
tw
vol
Cough
Maximal
Sniff
Twitch
Voluntary
Stimulation Descriptors
ELS
MS
Ant MS
CMS
fMS
PNS
EMG
PMG
M-wave
Electrical stimulation
Magnetic stimulation
Anterior magnetic stimulation
Cervical magnetic stimulation
Focal magnetic stimulation
Phrenic nerve stimulation
Electromyogram
Phonomyogram
EMG response to PNS
Lung Volumes
FRC
RV
TLC
VC
General
CNS
HFF
LFF
MVC
SMVC
Principles
ELECTROMYOGRAPHY
Rationale
Single motor unit action potential. Each motor unit is composed of a number of individual muscle fibers innervated by a
single anterior horn cell. All individual fibers within a motor
unit are activated almost simultaneously. The amplitude and
shape of the resulting motor unit action potential (MUAP)
are influenced not only by all the factors that can affect single
fiber action potentials, but also by such factors as the number
of fibers within the motor unit, the spatial dispersion of motor
unit fibers, differences in length of the motor neuron terminal
axons, and possibly fiber-to-fiber differences in action potential conduction velocity (2, 7).
Summation of motor unit signals. Compound muscle action
potentials (CMAPs) represent the summated electrical activity generated by all motor units synchronously activated by
nerve stimulation (see subsequent passages). The observed
CMAP is influenced by the number of activated motor units,
their synchronization, the shape of individual MUAPs, and
cancellation of opposite phase potentials.
The interference pattern EMG results from the temporal
and spatial summation of asynchronously firing MUAP trains
during spontaneous muscle contractions, when individual
MUAPs can no longer be distinguished (8). The observed interference pattern EMG is thus a function of the number of
active motor units, their firing rates and synchronization, the
shapes of their individual MUAPs (in turn dependent on all
the factors listed here previously), and cancellation of opposite phase potentials (2, 8).
EMG Equipment
549
Intramuscular electrodes
Advantages
Disadvantages
Noninvasive
Large volume sampling
Cross-talk
Variable filtering
Discomfort
Unreliable in diaphragm hernia
Discomfort
Difficult to place
Small pneumothorax risk
Possible sampling error
but no standards exist for electrode design or positioning. Furthermore, there is no consensus on methods either to maintain
electrode orientation with respect to muscle fibers and innervation zones or to control for influences of variable muscle-toelectrode distance (as, e.g., with variations in the amount of
subcutaneous fat), or for cross-talk from adjacent muscles.
Advantages of surface electrodes are their noninvasive nature and their ability to sample a large number of motor units.
For many individual nondiaphragm respiratory muscles, however, their proximity to one another and to nonrespiratory
trunk muscles makes surface electrode recordings unreliable.
Examples include cross-talk from scalenes and platysma in recordings of sternocleidomastoids (9), from external oblique
and pectoralis in recordings of intercostal muscles, and among
various abdominal muscles (10, 11). Furthermore, variations
in interindividual body habitus, for example, subcutaneous fat
tissue or deformity of the chest wall, produce variable muscleto-electrode filtering effects.
Esophageal electrodes. Esophageal electrodes are metal electrodes mounted on a catheter, which is inserted via the nose or
550
est to the crural diaphragm at any point in the respiratory cycle. Application of a double subtraction technique using the
difference between signals obtained from each electrode pair
caudal and cranial to the crural diaphragm (19) further enhances the signal-to-noise ratio.
Advantages of esophageal recordings are that they are not
influenced by obesity and that, when used with or combined
into the same catheter as esophageal and gastric pressure monitors (12), they enable simultaneous recordings of diaphragm
EMG and transdiaphragmatic pressure. Disadvantages include
the discomfort and the remote risks of regurgitation, aspiration, and vagally mediated bradycardia associated with their
placement. Diaphragmatic hernia may be a source of error in
esophageal recordings. In theory, the EMG from esophageal
electrodes may not be representative of the diaphragm as a
whole, because it samples only the crural portions of the diaphragm. However, although cruralcostal dissociation during
breathing has been demonstrated in animals (20, 21), it appears not to be a problem in humans (2224).
Intramuscular electrodes: advantages. Intramuscular electrodes provide relatively selective recordings from nondiaphragm respiratory muscles (911, 2530) with sufficient discrimination of individual motor unit activity to allow evidence
of denervation or myopathy to be detected. Whitelaw and
Feroah (30) have provided a detailed description of a safe
method to record single motor unit activity in intercostal muscles with wire electrodes. A number of investigators have
demonstrated techniques for placement of monopolar or bipolar needle electrodes in the human diaphragm, either by a
medial subcostal approach (31, 32) or by a lower intercostal
approach (33, 34) (Figure 2), sometimes assisted by real-time
ultrasound. Fine wire electrodes for single motor unit recordings have also been implanted in the right hemidiaphragms of
humans (13, 35). Although the flexible nature of wire electrodes makes them relatively stable during volume changes of
up to 1.5 L around the FRC, artifactual changes in recording
conditions occur with larger volume changes (13). Wire im-
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551
Figure 4. (A) Needle EMG of the diaphragm of a patient with porphyric neuropathy, showing a few fibrillation potentials and positive wave
potentials, along with QRS complexes (calibration, 10 milliseconds/division and 100 mV/division). (B) Needle EMG of the same patient 4
weeks later, showing increased numbers of positive sharp waves and
fibrillation. Reprinted by permission from Reference 34.
scope equipped with a camera. A more versatile system, essential for frequency domain measurements, is a computer with
an analog-to-digital converter. Because in digitally sampled
signals only spectral components of frequencies lower than
half the sampling frequency can be observed (the Nyqvist theorem), the sampling frequency should be chosen accordingly.
To provide an analog signal proportional to average
EMG activity at any point in time, many investigators subject
the raw EMG signal to rectification and leaky integration.
Unless sophisticated analog gating and/or filtering techniques
are employed, however, the effects of multiple artifacts detailed in the following sections limit this technique to providing only a crude estimation of the level of muscle activation.
Data Analysis
Time domain EMG analysis. Time domain EMG analysis represents the electrical activity of the muscles as a function of time. At
low levels of contraction, isolated MUAPs can be distinguished
and analyzed by such time domain indices as signal amplitude and
different types of integrated EMG, including full wave rectified
and averaged signal (FRA) and root mean square of the signal
Mn =
P f
i
n
i
i=0
Filter effects. Muscle-to-electrode distance. Increasing muscleto-electrode distance results in reduced signal amplitude with
relatively larger attenuation of high- than low-frequency power,
552
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Figure 5. Time and frequency domain characteristics of diaphragm EMG signals obtained with bipolar esophageal electrodes
positioned near a region with low density
of motor end-plates and aligned in the direction of diaphragm fibers. Left: Raw EMG
and computed power spectrum from a
pair of electrodes with a 10-mm interelectrode distance. Right (top and bottom):
Signals derived at the same time from the
same region using electrodes with a 5-mm
interelectrode distance. Right (middle): On
the left is shown a cross-correlogram obtained from the successive cross-correlations at various time delays between EMG
signals obtained with a 5-mm interelectrode distance; on the right is shown two
motor unit action potentials (MUAPs) obtained from the two electrodes pairs with
a 5-mm interelectrode distance. Reprinted
by permission from Reference 46.
so that the relative distribution of power in the spectrum is altered and fc is reduced (1, 1417, 40) (Figure 6).
Interelectrode distance and alignment with respect to fiber
direction (bipolar arrangement). Both interelectrode distance
and the orientation of the electrodes with respect to fiber direction can affect power spectra (1, 18, 41). As shown in Figure 5, reductions in interelectrode distance reduce signal
Figure 6. The influence of esophageal electrode positioning on diaphragm EMG center frequency (fc) (left axis; circles) and root mean
square (RMS) (right axis; squares). Solid symbols indicate experimental
data, whereas open symbols indicate computer-simulated power spectra. The 0 on the x axis indicates the center of the electrically active
region (source). RMS was lowest at the electrode pair positioned directly over the source (due to the cancellation effect of a bipolar electrode). Caudal and cephalad to the source, RMS increased progressively to maxima at approximately 10 mm from the source in either
direction. fc was maximal at the electrode pair directly over the source,
hence less high frequency is filtered by the electrode being closer to
the muscle. Reprinted by permission from Reference 46.
553
See Table 2.
Single fiber and motor unit analysis. Single fiber and motor
unit signal analyses are useful for diagnosis of nerve or muscle
pathology. For the diagnosis of neuromuscular disease, limb
muscles are more commonly studied than respiratory muscles,
because they are more readily accessible. A number of investigators have demonstrated the usefulness of needle electromyography of the diaphragm for the diagnosis of neuromuscular
disease, particularly neuropathic processes such as Guillain
Barr syndrome, lower motor neuron involvement with spinal
cord injury, and polyneuropathy of critical illness (31, 32, 34).
Bolton (34) has pointed out that the relatively high-frequency, low-amplitude potentials of the normal diaphragm
are often difficult to differentiate from myopathic potentials.
Nevertheless, several neuromuscular diseases present primarily with respiratory muscle weakness; as experience is gained
with single fiber and motor unit analysis of respiratory muscles, these techniques applied to respiratory muscles may provide the earliest evidence of the neuro- or myopathic process.
Condition
Denervation
Demyelination
Chronic denervation
Myotonia
Myopathy
Paralysis or dyscoordination
Quantification of neural drive
Efficiency of contraction
Fatigue
Finding
MUAPs, fibrillation potentials, and
positive sharp waves
MUAPs, without potentials
No., size of MUAPs
Myotonic discharges
Short, polyphasic potentials
Respiratory muscle activation pattern
Changes in FRA or RMS
Pdi/Edi
Spectral analysis
Definition of abbreviations: Pdi/Edi ratio of tidal respiratory change in transdiaphragmatic pressure to tidal respiratory change in integrated diaphragm EMG; EMG electromyography; FRA full wave rectified and averaged signal; MUAP motor unit action potential;
RMS root mean square of the signal.
554
STIMULATION TESTS
Rationale
Peripheral nerve, spinal, or cortical stimulation, either by implanted electrodes (for peripheral nerves) or by externally applied electric or magnetic fields, elicit relatively synchronized
activation of motor units at reproducible and predictable levels. The resulting compound action potentials and subsequent
muscle contraction allow for measurement of the efficiency of
neural and neuromuscular transmission. The muscle responses
to stimulation are discussed in PHRENIC NERVE STIMULATION in
Section 2 of this Statement.
Scientific Basis
Nerve stimulation. Stimulation of respiratory nerves can be accomplished with electrical or magnetic stimulators (Table 3).
The former are less expensive, less cumbersome, more rugged,
and more precisely controllable; the latter are easier to apply and
less painful for patients. For electrical stimulation, the phrenic
nerve is stimulated transcutaneously by surface electrodes at the
posterior border of the sternomastoid, or with implanted needle,
wire, or hook electrodes. The phrenic nerve(s) can also be stimulated magnetically, via a dorsal cervical approach, which stimulates the lower cervical nerve roots; via an anterior presternal approach, which stimulates both phrenic nerves; or, using one or
two figure-of-eight coils, unilaterally or bilaterally over the anterior neck to stimulate one or both phrenic nerves.
Several other respiratory nerves and muscles can also be
stimulated, either transcutaneously or by needle or wire electrodes. Pradhan and Taly (28) have demonstrated a technique
for stimulating lower intercostal nerves via probe electrodes
for latency measurements. The ventral roots of intercostal
nerves have been stimulated either by high-voltage stimulation over the spine (6466) or by surgically implanted wire elec-
Advantages
Disadvantages
Electrical
Implanted
Difficult to place
Transcutaneous
Inexpensive
Requires little preparation
Painful
Difficult to maintain contact
during voluntary effort
Magnetic
2002
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Nerve stimulation is essential for measurements of nerve conduction velocity or latency. Furthermore, the electromyographic
555
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Applications
Figure 8. Effects of cortical stimulation at rest and during voluntary inspiratory efforts of varying strength. Left: Transdiaphragmatic pressure
(Pdi) twitches obtained by bilateral supramaximal phrenic nerve stimulation during relaxation (thick trace). The thin traces show twitches resulting from transcranial magnetic stimulation (stimulator set at 85%
maximal) at rest (lowest trace, no twitch) and during three graded
static inspiratory efforts. Note the facilitation of Pdi twitches at intermediate voluntary efforts and the partial occlusion at high effort. Right:
Compound muscle action potentials (CMAPs) recorded from surface
electrodes on right and left chest wall (over the diaphragm) during
magnetic stimulation at the four levels of voluntary effort shown at
left. Note the progressive facilitation in CMAP amplitude. Reprinted by
permission from Reference 76.
Normal phrenic nerve/diaphragm latencies, elicited by electrical stimulation at the neck, have been reported to average 68
milliseconds in adults (12, 16, 82, 83), with lower values in children (see Table 4). Because the right phrenic nerve is shorter
than the left, latency is slightly shorter on the right side.
CMAP amplitudes, recorded from chest wall surface electrodes, average 500800 mV. Normal values for magnetic
stimulation-induced phrenic nerve/diaphragm latency or for
intercostal nerve/muscle latency have not been fully established (84, 85).
Phrenic nerve/diaphragm latencies are abnormally slow in
demyelinating polyneuropathies, notably Guillain-Barr syndrome. They are usually nearly normal, but are associated
with markedly depressed CMAP amplitude, in traumatic neuropathies, such as postcardiac surgery phrenic nerve palsy or
the polyneuropathy of critical illness. In myasthenia gravis, a
reversible decrement in diaphragm CMAP can be elicited by
repetitive phrenic nerve stimulation.
CCTs from cortex to phrenic motoneurons are approximately 4 milliseconds in normal adults (35). Normal values for
D- and I-wave amplitudes and the effects of disease are not
yet established, but it is apparent that I-wave amplitude is reduced by general anesthetic agents.
Transcranial stimulation to determine CCT has been used
in the assessment of a range of upper motor neuron disorders
and particularly in the assessment of patients with possible
CNS demyelination, including multiple sclerosis. It can be applied specifically to the respiratory muscles, or, more commonly, to muscles in both upper and lower limbs.
Compound muscle action potentials (CMAP) in response
to electrical or magnetic nerve or cortical stimulation can also
provide useful information. Lack of a CMAP after nerve stimulation is an indication of paralysis, with the lesion located
proximal to or at the neuromuscular junction. Lack of a
CMAP in response to cortical stimulation when a CMAP is
elicited by phrenic nerve stimulation has been used to identify
good candidates for phrenic nerve pacing.
Changes in CMAP amplitude, especially as compared with
changes in elicited muscle twitch strength (such as phrenic
stimulation-induced diaphragm CMAP as compared with
transdiaphragmatic twitch pressure [Pdi,tw]) can be used as
evidence for or against the development of neural or neuromuscular transmission defects (when both Pdi,tw and CMAP
decrease) or contractile defects (when Pdi,tw decreases but
CMAP does not) (86).
CONCLUSION
In a manner analogous to the use of the electrocardiogram to
assess cardiac function, electrophysiological tests of respiratory musclesrespiratory muscle motor latencies and elec-
Abnormal in:
68 ms
Elicited CMAP
4 ms
Multiple sclerosis
557
tromyographycan be used to assess (1) respiratory drive, respiratory muscle coordination, and the level of activation of
individual muscles; (2) the presence of neural and neuromuscular pathology; and (3) the apparent efficacy of the contractile function of the muscles, when used in conjunction with
measurements of contractile force. The special challenges presented by data analysis complexity and by a host of potential
artifacts lead to the need for great care in the application of
EMG techniques to respiratory muscles. Nevertheless, neurophysiological tests are emerging as indispensable components
of the respiratory muscle physiologists arsenal.
SUMMARY
This Section of the Statement has described available electrophysiologic tests, the functions of which are to assess the integrity of the respiratory neuromotor apparatus. These electrophysiologic tests are technically complex and require considerable
expertise.
There are two main types of test: electromyography (EMG)
and stimulation tests.
Type 1: EMG. For the respiratory muscles the EMG can
be used to assess the level and pattern of activation, to detect
and diagnose neuromuscular pathology, and when combined
with tests of mechanical function to assess the efficacy of contraction.
The EMG can be recorded with surface electrodes (for diaphragm, intercostal, scalene, abdominal, and accessory muscles) or an esophageal electrode (for the crural diaphragm).
Surface electrodes are noninvasive and sample a large number
of motor units, but contamination (cross-talk) from other
muscles is a substantial problem, as is the effect of body size
and shape on signal amplitude. Esophageal electrodes provide
more specific information, but the technique is invasive and
complex.
Surface and esophageal electrodes can record the interference pattern EMG (raw EMG) of the respiratory muscles and
are useful to determine the timing and level of respiratory
muscle activation during breathing, at rest, and under load.
Frequency domain analysis of the EMG is used, as a research
tool, to investigate respiratory muscle fatigue (discussed in
Section 5 of this Statement).
Intramuscular electrodes can be used to record, relatively
selectively, from the diaphragm and intercostal muscles. Motor neuron firing frequency can be measured and neuromuscular disorders diagnosed. However, the techniques are invasive and technically difficult.
Type 2: Stimulation Tests. Stimulation tests measure the
efficiency of neural and neuromuscular transmission.
Nerve stimulation can be achieved with electrical or magnetic stimulators. Electrical stimulation is inexpensive and relatively selective, but is uncomfortable and can be technically
difficult. Magnetic stimulation is easier to achieve and less uncomfortable, but can be less selective and is expensive.
Most commonly the phrenic nerves are stimulated and the
diaphragm EMG elicited, for the measurement of phrenic
nerve/diaphragm latencies and CMAP amplitudes. Latencies
are prolonged in some neuromuscular disorders (e.g., demyelination) and CMAP is reduced in amplitude (e.g., traumatic
damage to the phrenic nerves).
Cortical stimulation is most commonly performed with a
magnetic stimulator, and permits the measurement of central
conduction times (CCT) for limb muscles and diaphragm.
CCT can be prolonged as, for example, in multiple sclerosis.
Cortical stimulation is not selective, and the application of the
technique to the respiratory system is a highly specialized skill.
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Many different kinds of tasks have been used to quantify the endurance properties of the respiratory muscles. Most often, endurance has been defined in terms of the ability to sustain a level of
minute ventilation (ventilatory endurance) or a level of inspiratory
and sometimes expiratory pressure. However, these simple measures often present limitations to evaluating the effect of the load
on the respiratory muscles. From a muscle energetics viewpoint,
the energy requirements of a working muscle (and therefore a
rough estimate of its level of activation) are determined largely by
the tension developed over time (i.e., tensiontime product) and
(1)
(2)
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( VO2,rs) (15, 16) have been shown to be significantly correlated to changes in PTI (Figure 2). Furthermore, PTI is a parameter that describes the pressure-generating activity of the
muscles, independent of a specific breathing rhythm, breathing frequency, or type of load within the experimental limits
tested (1). Normalizing to maximum pressure can also be useful as a measure of the amount of pressure reserve utilized
during contraction. For example, most normal subjects can
sustain a PTIdi of up to approximately 0.18 (1) and a PTI for
the chest wall muscles and the synergic inspiratory muscles of
up to approximately 0.3 (2). These critical PTI values may
be useful in estimating whether the muscles are undergoing
contractions that are likely to lead to a loss of force, or fatigue (17, 18). However, critical PTI should be used with considerable caution, as it is highly likely that the critical PTI may
vary somewhat across various pathological conditions. This
has not been studied extensively. In addition, in clinical situations there is often some uncertainty regarding the accuracy of
measurements of PI,max or Pdi,max used to calculate PTI (see
VOLITIONAL TESTS OF RESPIRATORY MUSCLE STRENGTH in Section 2 of this Statement).
Disadvantages. When
the level of ventilation increases at a
constant PTP, the VO2,rs is increased and endurance is reduced (15, 19). For example, in Figure 3A, when a subject is
inspiring with a constant PTP (individual isopleths), increasing
flow rates result in markedly
increased oxygen consumption
(Wrs), discussed below, begins to take on a greater significance (19). As shown in Figure 3C, when ventilation is al
lowed to vary over
a wide range of PTP, Wrs becomes highly
against an external load (Wext) may provide sufficient information for purposes of respiratory muscle endurance testing.
If a subject is breathing against an external load and ventilation remains near spontaneous levels during loading, the
rate of work performed against the lung and chest wall remains relatively unchanged from normal breathing. There
fore, any changes in Wrs can be attributed largely to
changes in the work performed against the external load, or
where VI inspiratory minute ventilation. Equation 3 emphasizes one of the reasons why measures of the pressuretime product are so powerful in predicting endurance and
changes in en
ergy consumption during external loading. If VI stays constant,
561
The use of Equation 3 eliminates the necessity of performing complex integrations of individual pressurevolume loops
for each breath, which are required for more sophisticated es
timates of the total Wrs, discussed below. Therefore, it is pos
sible to measure changes in Wext, online, with digital or electronic multiplication of Pmo and VI.
An additional component of Wext occurs from gas compression (expiration) or decompression (inspiration) when large
pressures are generated in the airways (15). During inspiratory
loading, this gas decompression can account for as much as 0.4
L of displaced tidal volume in normal subjects, elevating the
work of breathing by as much as 50%. If thoracic volume is
measured in a volume displacement box, this additional volume
is measured directly. However, it can
also be calculated. Appro
priate equations for adjustment of VI for gas decompression depend on the nature of the loading device (15, 19, 21). For example, if a threshold loading device is used, in which inspiratory
pressure generation is approximately constant, the inspired
minute ventilation can be adjusted appropriately by adding the
decompression volume calculated in the following way:
VT,I = ( FRC + VT,I ) [ 1 ( Pbs Pmo
P H O ) ( Pbs P H O ) ]
2
(4)
determinant of both energy consumption of the muscles and endurance time (Figure 3). For ventilatory endurance testing, mea
surements of Wrs overcome the problems of variability in lung
and chest wall impedance between subjects and in the same subjects over time. Such changes in lung mechanics are inevitable
in patients who may have wide diurnal variations and fluctuations over more extended time periods. Therefore, measurement
of Wrs may be necessary to draw appropriate conclusions regarding the endurance properties in various patient groups. To a
large extent, these studies have yet to be systematically performed.
comprehensive relationship between Wrs, P, VO2,rs, and endurance for the respiratory muscles could be derived for all loading
conditions. From an energetics standpoint, the relationship between them is roughly described for the inspiratory muscles by
Equation 5:
O ,rs = W
rs Ers = ( Pmus V
I ) Ers
V
2
(5)
VI, the energetics and presumably the endurance of the respiratory muscles could be predicted. Unfortunately, Ers is not particularly constant at different relative velocities of muscle shortening (24) or at differing ventilations, depending on the way
breaths are performed (21), making this ideal difficult to obtain.
562
by its mathematical
contribution to Wrs or its energetic contri
bution to VO2,rs.
The goal of ventilatory endurance testing is to define the maximum sustainable ventilation (MSV), usually expressed as a
fraction of maximal voluntary ventilation (MVV). The time
duration needed to define sustainable is a topic of some controversy and varies with the specific technique described below. As shown in Table 1, normal subjects can sustain ventilations ranging from 60 to 80% of MVV. Therefore, with
submaximal exercise, it is probably rare that any normal individuals ever exceed their MSV, because maximum exercise
ventilations average approximately 61 14% of MVV in the
normal population (31). In some athletes, ventilation is maintained near the sustainable level of sedentary subjects. For
example, elite cross-country skiers can sustain ventilation averages during exercise in excess of 100 L/minute, or approximately 61% of their predicted MVV for periods of 30 to 85
minutes (32), with little or no evidence of fatigue. However,
the baseline MVV in these athletes is frequently elevated above
normal, and unlike normal subjects, they can sustain 8690%
of MVV for 4 minutes, presumably because of their extreme
conditioning. In a clinical setting, the measurement of ventilatory endurance takes on a much greater importance because
patients with chronic lung disease or perhaps heart failure (4)
may progress to a condition in which exercise is limited by
their ability to sustain ventilation. The ventilatory endurance
test is a measure of both inspiratory and expiratory muscle endurance.
Methodology
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(32). Although a potentially useful and practical approach, insufficient data are available to evaluate whether this provides
a sufficient estimate of sustainable ventilation. In all studies, it
is necessary to control end-tidal carbon dioxide (PETCO2) during the test, usually by adjustment of the carbon dioxide fraction (FCO2) in the rebreathing dead space. The average ventilation achieved over the last minute is considered
to be the
Subject Age
(yr)
26 2
31 1
31 3
31 3
67 4
(estimate)
50 1
No. of Subjects
Subject Sex
(No. F/M)
MSV/MVV*
(%)
16
14
12
5
25
16/0
0/14
1/11
0/5
14/9
60 8
62 9
80 6
75 4
63 11
1/7
55 9
Definition of abbreviations: F female; M male; MSV maximum sustainable ventilation; MVV maximum voluntary ventilation.
* Results represent means SD.
563
ments nearly identical to those that could be attained by traditional approaches, and was well tolerated by subjects (4).
The importance of sustaining a maximum ventilation for the
three or more minutes at the end of the test should be emphasized. Presumably, during this period, fatigue of the respiratory muscles is progressing rapidly because it is a period of
maximum effort following a relatively long period of nearmaximum effort. Presumably this results in a decay of ventilation to a near sustainable level.
Normal Values
Normal values for MSV, by any method, have not been systematically obtained over a wide population, and results vary
considerably between laboratories (Table 1). The large differences in predicted values may be due in part to variations in
technique, particularly with respect to impedances of the mechanical measuring devices. The system impedance can have
substantial effects on the total Wrs at high ventilations. In addition, there are differences in the populations studied and
what was defined as sustainable. It is recommended that when
publishing reports of ventilatory endurance, the value for the
impedance of the measuring device be stated. Until more
complete population standards and uniform equipment and
techniques are available, each laboratory is advised to establish its own population standards.
Results for MSV should be reported as a fraction of measured MVV (MSV/MVV%) and either as an absolute value
(L/minute) or as a fraction of predicted MVV (MSV/MVV%
pred). The latter, which has not been used routinely, provides
a normalization of the absolute sustainable value to the patients age, height, and sex, independent of inherent lung or
respiratory muscle function.
Advantages
There are a number of advantages to measuring MSV as an indicator of respiratory muscle endurance, the most important
of which is its close resemblance to the task performed during
exercise. It therefore provides clinically relevant data that can
be related to function. Second, it is probably a measure of
both inspiratory and expiratory muscle endurance because in
normal subjects there appear to be decrements in both inspiratory and expiratory function after MSV maneuvers (39).
Finally, maximum ventilatory maneuvers result in evidence of
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Figure 6. Relationships between power output, ventilation, and endurance time (Tlim). Solid line: Maximum voluntary ventilation. Dotted
line: Calculated work rate or power output of the respiratory muscles.
Redrawn by permission from Reference 33.
565
566
having an overall outcome that is little affected by the breathing pattern (56). However, subsequent testing by Eastwood
and coworkers (57), using similar techniques, found that normal subjects demonstrate a considerable learning effect from
the first to the third trial.
the final stages of the test. It is promising that peak Wext may
be a useful measurement of the capacity of the muscles of the
chest wall to perform external work, a value that may be as
important clinically as the measure of endurance. A second interesting finding is that some subjects are able to achieve
higher Ppeak values during this test than they can attain during PI,max maneuvers (50, 53, 57), a phenomenon attributed
to the fact that some subjects are unable to maximally activate
their inspiratory muscles during PI,max testing (58).
Disadvantages. Unfortunately, the extent to which the results from incremental tests represent endurance or strength is
not entirely clear. Strictly speaking, it is not a test that has been
proven to be a direct measure of endurance, just as an incremental exercise test is not generally considered an endurance
test. However, when individuals are asked to attempt to sustain
the maximum threshold pressure previously reached with the
incremental method, the average Tlim they can maintain is approximately 6 minutes (53). This suggests that although the
maximum incremental threshold pressure is not sustainable, it
is certainly approaching the asymptote of a typical inspiratory
muscle endurance curve. Another suggestion that the threshold
test is approximating an endurance measurement is the fact that
the maximum PTImo in the last stage is approximately 0.22
0.32 (50, 57), which is similar to sustainable pressures described
for the rib cage muscles (2) and the inspiratory muscles working
in synergy in a normal range of duty cycles and low flow (13).
Of some concern is the tendency for hypoventilation and
desaturation during the test (57). Although modest desaturation is unlikely to affect the measurement appreciably in normal subjects (57, 59), hypercapnia may contribute to a loss of
function, unrelated to endurance characteristics (60, 61). Finally, as the intensity of the load increases, subjects consistently decrease end-expiratory lung volume to maximize the
length and configuration of their inspiratory muscles (57).
This is something of a disadvantage for testing, because the capacity of the muscles to contract against the load is changing
during the test. However, it is likely that such changes in configuration are typical of patient responses to many types of
high inspiratory mechanical or ventilatory loads and is not a
problem unique to incremental loading. Finally, the recruitment patterns of the respiratory muscles may vary during incremental loading and may not totally reflect the endurance
characteristics of breathing against constant submaximal loads.
Repeated Maximum Inspiratory Pressures
Methodology. McKenzie and Gandevia (6, 62, 63) have developed a technique that uses 18 repeated PI,max maneuvers.
The test begins with measurement of PI,max and practice efforts using visual feedback of airway opening pressure. Three
different breathing patterns have been described (6, 62). The
most practical appears to be a series of 18 PI,max contractions
lasting 10 seconds each, with 5 seconds of rest between contractions (duty cycle 0.67) (62). A similar approach has
been used to measure expiratory and limb muscle endurance
(6). The only equipment required is a manometer for measuring airway opening pressure. This technique has been generally used to measure inspiratory muscle endurance.
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567
Author (Ref.)
Age
(yr)
Subjects No.
(M/F)
PTIpeak
Martyn (50)
33 2
14 (9/5)
88 10
NR
McElvaney (53)
31 5
10 (5/5)
0.22 0.07
0.25 0.08
Morrison (56)
67 4
8 (5/3)
Trial 1:
84 17
Trial 2:
87 21
80 17
Eastwood (57)
30 (2841)
7 (5/2)
Trial 1:
75 20
Trial 3:
94 21
0.32 0.12
NR
0.26 0.11
Definition of abbreviations: F female; M male; NR not reported; PI,max maximum inspiratory pressure; Ppeak peak threshold
pressure achieved during incremental loading under conditions stated in Notes on End Point column; PTIpeak peak pressuretime index
achieved during incremental loading under conditions stated in Notes on End Point column.
* Results represent means SD.
Mean (range).
Figure 8. (A) Equipment used for the isoflow loading device. The tanks
and regulators on the left provide a high-pressure source through an
extremely high resistance. Flow is activated by a pressure-triggering
device. The oscilloscope provides visual feedback, so that the subjects
can perform maximally. CO2 is maintained at a constant value by supplementing the inspiratory gas. (B) A typical endurance curve from an
isoflow test. Open circles: The peak pressure developed during inspiration. Open triangles: The average pressure generated during inspiration
per breath. Reprinted by permission from Reference 64.
568
sustainable level of P and Wrs. Further studies in patient populations will be required to determine the comparative usefulness of these techniques in a clinical environment.
All of the external loading techniques are more likely to reflect the endurance qualities of the rib cage muscles as compared with the diaphragm (44, 57, 66). This should be kept in
mind with regard to their clinical implications.
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Measurements of diaphragm endurance have not been routinely performed in a large number of normal subjects. However, Bellemare and Grassino (1) described the normal sustainable PTIdi to be in the range of 0.150.18 when tidal
volume remained approximately 0.75 L (Figure 2A). Therefore, at a duty cycle of approximately 0.4, normal subjects can
sustain approximately 4050% of Pdi,max.
Advantages
Methodology
Disadvantages
Roussos and coworkers (45) tested for the maximal sustainable, transdiaphragmatic load. Subjects sustained a given Pdi
until they could no longer reach the target pressure. There
were no requirements on breathing frequency or duty cycle.
They found that approximately 40% of Pdi,max could be sustained for 6090 minutes. A higher Pdi lasted for a shorter
time.
A more precise technique for measurement of diaphragm endurance in humans was developed by Bellemare and Grassino
(1, 67). Subjects are instrumented with an esophageal and gastric
balloon as described in PRESSURE MEASUREMENTS in Section 2 of
this Statement. Maximum transdiaphragmatic pressure is determined and then subjects proceed to inspire through a variable inspiratory flow resistance with a set breathing pattern by
watching an oscilloscope (Figure 9). Two target pressures are
displayed on the oscilloscope screen: Pdi and gastric pressure
(Pga). Tidal volume and duty cycle (TI/Ttot) are monitored as
well. The subject generates a target Pdi by actively inspiring
against a variable resistance and a target Pga of approximately
50% of Pdi. Runs with Pdi of 0.2 to 0.8 and TI/Ttot of 0.2 to 0.7
were tested. The product of Pdi/Pdi,max TI/Ttot was found
to be the best predictor for endurance. Values of 0.15 to 0.18
or smaller could be sustained for more than 1 hour. Values
Because of the need for invasive instrumentation and the requirement of the subject to coordinate a rather unnatural pattern of abdominal and thoracic expansion, the technique has not
been applied extensively to the clinical environment. PTIdi
was measured in patients being weaned from a ventilator. It
shows that patients developing a PTIdi higher than 0.18 failed
the weaning trial. The same patients were tested at a later date
with favorable evolution and had a PTIdi below 0.15, and they
could be weaned (68). One potential complication lies in the
fact that diaphragm blood flow may be determined in part by
the relative negative or positive pressures on its surface. For
example, Buchler and coworkers (30) demonstrated that blood
flow is obstructed more by high positive abdominal pressures
than by similar Pdi values obtained by negative pleural pressures. This would suggest that by contracting the abdominal
antagonist muscles simultaneously with inspiration, there may
be reduced blood flow to the diaphragm, resulting in a greater
probability of fatigue and a lower endurance.
In summary, for a specific measure of diaphragm endurance, the technique of Bellemare and Grassino (1) remains the
only method currently available. The methodology may become more accessible in the clinical environment as techniques develop for rapidly attaining a measure of sustainable
Rationale
569
PTIdi, using incremental or maximum effort approaches similar to those described for global inspiratory muscle function.
This technique remains in the domain of clinical research. Few
studies are available.
CONCLUSION
This Section of the Statement has explored the available techniques to assess respiratory muscle endurance. The measurements and techniques include the following:
1. Pressuretime product (PTP): The integration of inspiratory pressure swing over time. Pressure can be esophageal,
Pdi, or mouth pressure (if an external resistance is added to
the circuit). PTP of the expiratory muscles can also be measured. If pressure is normalized to a fraction of the maximum pressure, the value obtained is the pressure time index (PTI). A PTI of 0.150.18 is the upper limit that can be
sustained indefinitely by the diaphragm in humans and as
high as 0.3 for the rib cage muscles. The PTI thresholds are
lower if inspiratory flow is high.
2. Work of breathing: Calculated by the integration of pressure on tidal volume, measures work against an external inspiratory or expiratory load and is a useful test for measuring endurance as a function of workload. Values of work of
breathing relate well to oxygen consumption over a wide
range of ventilations. This measurement is limited to respiratory research and could benefit from computerized equipment to facilitate measurement and analysis in the clinical
setting.
3. Ventilatory endurance tests: Maximal sustainable ventilation (MSV) expressed as a percentage of 12 seconds of
maximum voluntary ventilation. Two techniques are available to determine MSV: the maximum effort technique
(the subject seeks to sustain ventilation at a target level of
7090% MVV for 8 minutes) and the maximum incremental technique (starting at 20% MVV, the target ventilation
is increased by 10% every 3 minutes). There are limited
normal data for MSV and these show considerable variability. Each laboratory should develop its own normal values.
MSV can be difficult to interpret (e.g., in patients with
COPD). The incremental technique may prove to be of
value in the clinical setting. To date, most studies of ventilatory endurance have been undertaken within a research
context.
4. Endurance of external loads applied to the airway: The external load can be resistive (the pressure required depends
on flow), elastic (pressure depends on tidal volume), threshold (finite pressure required to open the valve, which is independent of flow and volume), or an isoflow load (flow
rate held constant). The most widely used technique is that
of threshold loading. Either the maximum sustainable threshold load or the maximum incremental threshold load can
be measured. The incremental threshold loading test, which
uses the same principles as an incremental exercise test, is
the most commonly undertaken, and there are limited normal data available. It is not clear to what extent the test reflects respiratory muscle strength rather than endurance.
5. Repeated maximum inspiratory pressures: In this test the
subjects undertake 18 repeated PI,max maneuvers, each effort lasting 10 seconds with a 5-second rest between contractions. Pressure drops to 87% of PI,max in young normal
subjects over the run. Equipment is simple, and only a manometer and stopwatch are required. Few data from studies in patients are available.
6. Maximal sustainable isoflow: In this test the subject breathes
against a high impedence (air tank) providing a constant
flow (1 L/second). The subject develops maximal pressure
at a TI/Ttot of 0.40. Maximum pressure declines exponentially to a sustainable level of 61%, yielding a PTI of 0.18.
This technique has not yet been tested in large populations.
It has potential as a method of training the inspiratory muscles as well as documenting their endurance.
7. Endurance of the diaphragm: This has been studied in normal
subjects by measuring Pdi and TI/Ttot, which were kept constant by following a pattern of pressure and timing displayed
on an oscilloscope. A PTI of 0.200.30 resulted in task failure
at an earlier time. The technique was developed as a physiologic study designed to measure the use of TTIdi as a parameter to evaluate the development of diaphragm fatigue.
Of the tests of ventilatory endurance available, the most
promising, in a clinical context, appears to be the maximum
incremental ventilation test. To specifically assess the endurance of the inspiratory muscles, relatively independently of
lung and chest wall mechanisms, the incremental threshold
loading test appears to be most useful.
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on human diaphragm fatigue. J Appl Physiol 1982;53:11901195.
2. Zocchi L, Fitting JW, Majani U, Fracchia C, Rampulla C, Grassino A.
Effect of pressure and timing of contraction on human rib cage muscle
fatigue. Am Rev Respir Dis 1993;147:857864.
3. Schulz L, Nagaraja HN, Rague N, Drake J, Diaz PT. Respiratory muscle
dysfunction associated with human immunodeficiency virus infection.
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7. Keens TG, Krastins IRB, Wannamaker EM, Levison H, Crozier DN,
Bryan AC. Ventilatory muscle endurance training in normal subjects
and patients with cystic fibrosis. Am Rev Respir Dis 1977;116:853860.
8. Morrison NJ, Richardson DPT, Dunn L, Pardy RL. Respiratory muscle
performance in normal elderly subjects and patients with COPD.
Chest 1989;95:9094.
9. Weiner I, Azgad Y, Weiner M. Inspiratory muscle training during treatment with corticosteroids in humans. Chest 1995;107:10411044.
10. Homsher E, Kean CJ. Skeletal muscle energetics and metabolism. Annu
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11. Rall JA. Sense and nonsense about the Fenn effect. Am J Physiol
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570
12. McCool FD, Leith DE. Mean airway opening pressure as an index of inspiratory muscle task intensity. J Appl Physiol 1986;60:304306.
13. Clanton TL, Ameredes BT, Thomson DB, Julian MW. Sustainable inspiratory pressures over varying flows, volumes, and duty cycles. J
Appl Physiol 1990;69:18751882.
14. Bellemare F, Wight D, Lavigne CM, Grassino A. Effect of tension and
timing of contraction on blood flow of the diaphragm. J Appl Physiol
1986;54:15971606.
15. Collett PW, Perry C, Engel LA. Pressuretime product, flow, and oxygen
cost of resistive breathing in humans. J Appl Physiol 1985;58:12631272.
16. Field S, Sanci S, Grassino A. Respiratory muscle oxygen consumption
estimated by the diaphragm pressuretime index. J Appl Physiol 1984;
57:4451.
17. Begin P, Grassino A. Inspiratory muscle dysfunction and chronic hypercapnia in chronic obstructive disease. Am Rev Respir Dis 1991;143:
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18. Bellemare F, Grassino A. Force reserve of the diaphragm in patients
with chronic obstructive pulmonary disease. J Appl Physiol 1983;55:815.
19. Dodd DS, Kelly S, Collett PW, Engel LA. Pressuretime product, work
rate, and endurance during resistive breathing in humans. J Appl
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20. McCool FD, McCann DR, Leith DE, Hoppin FG. Pressureflow effects
on endurance of inspiratory muscles. J Appl Physiol 1986;60:299303.
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TYPES OF FATIGUE
On an operational level, it has proven convenient to classify
fatigue into different types, with these different forms of fatigue representing different biophysical mechanisms of fatigue
development and with each type having different physiological characteristics (3). Several such classification schemes are
possible, but a widely employed convention is to classify fatigue as either (1) central fatigue, (2) peripheral high-frequency fatigue, or (3) peripheral low-frequency fatigue. We
review each of these types of fatigue in turn.
Central Fatigue
Central fatigue is a failure to generate force as a result of a reduction in motor output from the central nervous system. Peripheral fatigue refers to failure at the neuromuscular junction
or distal to this structure and is judged to be present when
muscle force output or velocity falls in response to direct electrical stimulation. Peripheral fatigue can result because of alterations in the neuromuscular junction, changes in propagation of the action potentials along the sarcolemmal membrane
or into the t-tubules, changes in excitationcontraction coupling, or because of other alterations within the muscle cell
(e.g., alterations in metabolism, changes in contractile proteins). Peripheral fatigue can be further classified into highfrequency and low-frequency fatigue on the basis of the shape
of the postfatigue muscle forcefrequency relationship. If fa-
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ble of detecting another. Moreover, the necessity to make serial measurements of an index of muscle force generation over
time to detect fatigue is a particularly difficult endeavor for
the respiratory system, because a large number of variables
(i.e., lung volume, thoracoabdominal configuration, muscle interaction) can vary over time. All these factors can influence
the relationship between muscle force and pressure generation.
As an example, consider the utility of measuring maximum
inspiratory pressure (PI,max) serially to detect respiratory
muscle fatigue. This parameter is highly effort dependent, and
time-dependent reductions could represent lack of motivation,
central fatigue, peripheral high-frequency fatigue, or simply an
alteration in lung volume and a resultant mechanical change in
the transduction of muscle force into pressure. In addition, failure of the PI,max to change does not exclude the development
of fatigue, because this test would not be suitable to detect lowfrequency fatigue. As a result, one must keep in mind the potential limitations of a given test for the detection of muscle fatigue. Most tests are suitable for detecting the presence of only
one component of muscle fatigue, and complete characterization of fatigue requires a complex series of assessments.
Rationale. Rapid shallow breathing, characterized by high breathing frequency and low tidal volume, commonly develops in progressive respiratory failure or in unsuccessful attempts to wean
from mechanical ventilation. These conditions are associated
with an increased ventilatory load and/or a reduced respiratory muscle capacity and may therefore potentially lead to respiratory muscle fatigue (see PREDICTION OF WEANING in Section 10 of this Statement).
Methodology and equipment. Breathing frequency can be
easily counted at the bedside and should be included in standard monitoring. Tidal volume measurements of intubated patients are commonly accomplished with the flow sensors built
into modern ventilatory equipment and can be displayed on a
breath-by-breath basis by these machines. Volume measurements can also be made with Wright respirometers and other
spirometric devices via a mouthpiece in nonintubated patients,
albeit mouthpiece placement can artifactually alter tidal volumes and respiratory patterns. To avoid such artifacts, it is
possible to noninvasively monitor tidal volume by respiratory
inductance plethysmography. Use of this and similar methods
is described in DEVICES USED TO MONITOR BREATHING: PNEUMOGRAPH, MAGNETOMETER, AND RESPIRATORY INDUCTIVE PLETHYSMOGRAPH in Section 6 of this Statement.
Advantages. Monitoring changes in breathing frequency
and tidal volume is simple and noninvasive.
Disadvantages. The relationship between fatigue and breathing pattern is complex. Moreover, rapid shallow breathing is
most likely a reflex response to an increase in the respiratory
workload (24) and not the consequence of respiratory muscle
fatigue per se (25). Thus, although rapid shallow breathing may
accompany respiratory muscle fatigue (2), it cannot be considered a specific marker of fatigue.
Applications. Monitoring breathing frequency and tidal volume represents a part of the routine respiratory surveillance of
patients, but these parameters should not be used as specific indicators of the development of respiratory muscle fatigue (see
BREATHING PATTERN in Section 10 of this Statement).
In the presence of pure low-frequency fatigue, force generation in response to high-frequency stimulation is unimpaired,
indicating that the contractile proteins are capable of generating maximal force provided that sufficient calcium is released
by the sarcoplasmic reticulum (SR). As a result, impaired
force generation at submaximal frequencies of stimulation
may represent either a reduced level of calcium availability
due to alterations in SR function or a reduction in the calcium
sensitivity of the myofilaments at submaximal calcium concentrations. Both changes have been demonstrated experimentally (16, 17). Reduced myofilament calcium sensitivity can be
produced experimentally by increasing hydrogen and phosphate ions (18). The explanation for impaired calcium release
by the SR during contractions is less well understood, and a
number of theories have been proposed to account for this
phenomenon (16, 1921).
Low-frequency fatigue has been demonstrated in the diaphragm and sternocleidomastoid muscles of normal subjects
breathing against high resistive loads (17, 22). Low-frequency
fatigue has also been shown to develop in the diaphragm of
normal subjects asked to sustain maximum voluntary ventilation for 2 minutes (23).
Implications of Different Types of Fatigue for Diagnosis
Although it is convenient to discuss the characteristics of central, peripheral high-frequency, and peripheral low-frequency
fatigue separately, it is likely that these various phenomena do
not occur in isolation during muscle activation. All three processes may be operating simultaneously when the respiratory
muscles confront an excessive workload, with the relative importance of each depending on the duration of respiratory
loading and other physiological variables (i.e., arterial pressure, arterial blood gas concentrations, nutritional state). Whereas
all three processes may participate in the acute response to
loading, both central and high-frequency fatigue resolve rapidly once fatiguing levels of muscle contraction cease, and only
low-frequency fatigue is likely to persist over minutes to hours.
Because muscle fatigue is a complex phenomenon, a test
that is well suited to detect one form of fatigue may be incapa-
Thoracoabdominal Motion
Rationale. The analysis of breathing movements gives some insight into the level of recruitment and function of the respiratory
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invasive techniques have been validated only in normal subjects. Transmission of brief pressure swings from the alveoli to
the upper airways is likely to be dampened in patients with abnormal lung mechanics.
Equipment. The pressure measurement system required
for sniffs is described in Section 2 of this Statement. Analysis
of the MRR is best done with a computer program (46).
Advantages. The measurement of inspiratory muscle relaxation rate is relatively simple and requires minimal cooperation from subjects. The sniff maneuver is easily performed by
most subjects and patients and does not need to be perfectly
maximal, provided that the MRR is expressed as percentage
pressure fall per 10 milliseconds. Sniffs should, however, be
performed as near to the maximal as possible, because the
MRR is effort dependent below 60% of maximal pressure
(47). The muscle relaxation rate slows at an early stage during
fatiguing contractions and may therefore indicate that inspiratory muscle fatigue is incipient.
Disadvantages. The relationship between changes in relaxation rate and force loss during fatigue is not understood. For
instance, the degree of force loss does not correlate with the
changes in relaxation rate and therefore cannot be inferred
from this parameter (45, 47). The rapid recovery of this index
with rest also poses practical problems of measurement in
clinical settings. The range of normal values for the MRR and
is wide, with overlap between fresh and fatigued states. Serial measurements are thus required to detect the onset of inspiratory muscle fatigue in an individual (45). Finally, some
clinical conditions (e.g., asthma) have been reported to elicit
activation of inspiratory muscles during expiration (postinspiratory inspiratory muscle activity). Under such circumstances,
persistent activation of some muscles or portions thereof would
576
Time domain analysis. Rationale. For the respiratory muscles, as for any other skeletal muscles, a nearly linear relationship may be found between the pressure and the electrical activity they generate. The slope is related to force and the
length of the diaphragm. As a result, for a given muscle length,
a decrease in the ratio of respiratory muscle pressure to the integrated electromyographic activity of the muscle generating that
pressure should, in theory, indicate a decrease in muscle contractility and the development of fatigue. Furthermore, it has been
suggested that a decrease in this ratio indicates an alteration in
excitationcontraction coupling (50). This point is also discussed
in INFERRING DIAPHRAGM ACTIVATION AND ELECTROMECHANICAL
EFFECTIVENESS FROM EMG in Section 6 of this Statement.
Methodology. The methodology required for electromyographic assessment is reviewed in detail in EMG EQUIPMENT
AND DATA ANALYSIS in Section 3 of this Statement.
Advantages. In theory, this is a useful approach for separating changes in pressure-generating capacity caused by neural or neuromuscular transmission factors from changes caused
by peripheral muscular factors (51). One potential major advantage of this test is the possibility to detect fatigue during
spontaneous breathing (52), because no special efforts are required by patients.
Disadvantages. For this index to be valid, other factors affecting respiratory muscle contractility, such as muscle length,
chest wall configuration, or lung volume, should be controlled or
kept constant (53). The applicability of this particular method
to the respiratory system is limited by the difficulty of recording the activity of all the muscles involved in normal or augmented breathing that contribute to the measured pressure.
Their relative contribution to the generated pressure is known
to change during fatigue development (6, 28), and a reliable recording of the activity of a selective respiratory muscle group
is regarded as difficult by some (54). Section 3 of this Statement offers a more optimistic view. In practice, the diaphragm,
the neck accessory muscles, and the abdominal muscles are
most amenable to this form of testing because their electrical activity can be more easily recorded without interference from
other muscles and their force production (sternomastoid) or
pressure output (diaphragm and abdominals) can also be recorded in relative isolation.
When interpreting results, one must also recognize that the
relationships between integrated EMG activity of the respiratory muscles and the pressure they generate may not be perfectly linear (49).
If special precautions are not taken, EMG signals (particularly those recorded from the diaphragm with an esophageal
electrode) can be subject to artifactual changes caused by variations in lung volume or chest wall configuration (55). Luckily,
reports provide techniques that exclude many of the artifacts
associated with esophageal diaphragmatic recording. Specifically,
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Figure 4. Time course of various parameters during an isometric contraction held at 40% of maximal force (task) until failure. From the
top: Maximal force: voluntary maximal electrical supramaximal pulses
of the nerve. The vertical lines are pressure swings obtained by electrical stimulation, showing a progressive loss of maximal force. The time
elapsed from the start until task failure is known as the time limit, or
endurance. The exercise is defined as a fatiguing task, because there
was loss of maximal force. Regaining the ability to develop maximal
force takes a few minutes. Regaining the ability to perform the same
task again, however, takes hours. This panel shows the time course of
the central frequency (CF) of the EMG obtained via surface electrodes
and fast Fourier transforms in the same exercise. Decay of CF is fast,
and is a forewarning of task failure. This parameter is an expression of
membrane potential conduction velocity. Relaxation rate: The time
course of relaxation time (if the contraction is interrupted). Control
values are the same as in a rested muscle. This parameter is linked to
failure at the sarcomere level, mainly related to calcium coupling and
release from troponin. Tetanic force: The decrease in force during an
electrical stimulation at 100 or 20 Hz, and its ensuing rate of recovery.
Recovery from fatigue is faster when the muscle is probed with 100 Hz
than with 20 Hz; the former is proposed to be caused by conduction
mechanisms, whereas the latter is mediated by contraction mechanisms. Spontaneous shortening: Spontaneous shortening of the diaphragm before (100%) and after task failure, and time of recovery.
Figure used by permission from Dr. A. E. Grassino.
577
muscle under loaded conditions, can be most specifically detected by recording the pressure or forcefrequency curve of
that muscle in response to artificial motor nerve stimulation.
Of the respiratory muscles, the diaphragm (16, 65) and the
sternomastoid (66) muscles are most amenable to this form of
testing. Low-frequency fatigue has been documented for these
muscles in normal subjects during loaded breathing (16) as
well as during intense exercise (67).
Methodology. The methodology required for phrenic nerve
stimulation and sternomastoid stimulation is reviewed in detail in Section 2 of this Statement.
Advantages. This technique overcomes many of the difficulties associated with volitional or spontaneous breathing efforts. Indeed, the responses are not complicated by possible
variations in the level of effort expended. The response of a
particular muscle can also be studied in isolation, free from
the activity of other muscles. Changes in the shape of the pressure or forcefrequency curves also give indications as to the
underlying mechanism of fatigue. For example, a decreased
pressure or force at high stimulation frequencies may be indicative of impairment at the neuromuscular junction or at the
sarcolemma, whereas a decreased force or pressure at low
stimulation frequencies may suggest a possible impairment of
excitationcontraction coupling.
Disadvantages. This is a difficult test to perform. Tetanic
stimulation can also be painful and it may be necessary to
anesthetize the skin near the electrodes. To overcome this
problem, partial pressurefrequency curves may be constructed by using twin pulses and by varying the intervals between the pulses (68, 69). These are better tolerated than tetanic stimulation and can provide comparable information regarding
the presence of high- and low-frequency fatigue. Because of a
large intersubject variability in the responses to artificial stimulation, fatigue can be reliably detected by these techniques
only when a subject serves as his/her own control. A possible
exception concerns the ratio of the force or pressure developed at a low stimulation frequency (i.e., 20 Hz) over that at a
high stimulation frequency (i.e., 100 Hz), for which some critical value may be recognized below which low-frequency fatigue may be said to be present (16, 65, 66, 68).
Application. Although this test provides a means of directly detecting the development of muscle fatigue, applicability of this approach is limited by (1) patient discomfort associated with high-frequency stimulation, (2) equipment expense
and complexity, and (3) the need to carefully control for variation in body position, lung volume, and the electrodenerve
interface. Advances in magnetic stimulation techniques may
allow a variation of this form of testing to reach more widespread clinical application in the future, but this test is currently limited to research applications.
Single twitch stimulation. Rationale. As an alternative to
tetanic or twin pulse stimulation, recording of muscle twitches
in response to single nerve shocks can be employed to detect
the presence of low-frequency fatigue (68). Twitch responses
are much easier to obtain but are more variable than tetanic
responses and are subject to additional variations caused by
phenomena such as twitch potentiation (70).
Methods and equipment. The methodology required for phrenic
nerve stimulation is reviewed in Section 2 of this Statement.
Advantages. This technique is nonvolitional, eliminating
concerns about patient effort in the interpretation of obtained
results. In addition, because only single twitches are evoked
when employing this technique, much less patient discomfort is
involved when compared with that produced by construction of
the forcefrequency relationship. Because a single shock is, by
definition, a low-frequency stimulus, this approach also pro-
578
CONCLUSION
This Section of the Statement has reviewed the complex process of muscle fatigue and has discussed the available direct
and indirect measurements relevant to the assessment of fatigue of the respiratory muscles.
Although a variety of measures and indices have been employed to assess the development of respiratory muscle fatigue in
research, there is no well described technique that has been successfully developed and tested to permit precise identification of
respiratory muscle fatigue in the clinical setting. Of the tests reviewed, breathing pattern analysis and measurement of thoracoabdominal motion are nonspecific indices that do not directly
measure fatigue. Analysis of the pressuretime index provides a
useful conceptual framework, but not a specific test of fatigue.
In the research environment, serial measurement of maximal voluntary respiratory pressures, assessment of maximum
relaxation rates, frequency domain EMG analysis, and measurement of respiratory muscle pressures in response to electrical or magnetic nerve stimulation are all techniques that can be
used to assess the evolution of respiratory muscle fatigue. Of
these techniques, serial measurement of respiratory muscle
pressure generation in response to electrical or magnetic stimulation is arguably the best technique to directly assess the development of respiratory muscle fatigue at the present time, and it
offers the greatest promise for future development into an objective test of respiratory muscle fatigue in the clinical arena.
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Cervical magnetic stimulation: a new painless method for bilateral
phrenic nerve stimulation in conscious humans. J Appl Physiol 1989;
67:13111318.
74. Petitjean M, Bellemare F. Phonomyogram of the diaphragm during unilateral and bilateral phrenic nerve stimulation and changes with fatigue. Muscle Nerve 1994;17:12011209.
Scientific Basis
In respiratory mechanics, it is important to distinguish between the two uses of the word pressure. In one case it denotes a pressure measured at a given location, as in pleural
pressure. In the other case it denotes a difference in pressure
between two points, usually on opposite sides of a structure,
such as transpulmonary pressure, defined as the difference
between pressure at the airway opening (Pao) and pressure in
the pleural space (Ppl). Pressures are usually measured relative to barometric pressure (i.e., they are taken to be zero
when they are equal to barometric pressure).
Pressures at a point are usually assumed to be representative of the pressure in that space (see Figure 1 in Section 2 of
this Statement). This simplification must be qualified when
variations of pressure within a space are to be expected (1). In
particular, gravity causes vertical gradients in pressure related
to the density of the semisolid or liquid contents of a space: in
the thorax, this gradient is approximately 0.2 cm H2O/cm height
and is affected by lung density; in the abdomen, the gradient is
nearly 1 cm H2O/cm height. Temporal fluctuations in pressure, as in tidal breathing, are little affected by gravitational
gradients. Shear stress resulting from the deformation of elastic, shape-stable organs can cause local variations in pressure,
such as those that occur just below the diaphragm when it displaces the liver during a large forceful contraction (2).
Pressure differences across structures, as opposed to pressures measured at a point, are relevant for characterizing those
structures. The schematic drawing in Figure 1 of Section 1 of
this Statement shows relationships among locations where
pressures can be measured (within circles) and intervening respiratory structures and equipment (within rectangles). Pleural
and abdominal pressures are usually estimated by measuring
esophageal and gastric pressures (Pes and Pga), respectively.
Table 1 and Figure 1 in Section 2 of this Statement list pressures measured at a point and pressure differences across
structures. These differences are usually taken in a direction
such that positive pressure differences expand the structure
(e.g., lung). An exception to this rule is transdiaphragmatic
pressure (Pdi), which has been defined both as pleural pressure minus abdominal pressure, Pdi Ppl Pab, and as its reverse, Pdi Pab Ppl. The complicating effects of gravity
must be considered when pleural pressure is estimated from
esophageal pressure (Pes) and abdominal pressure is estimated from gastric pressure (Pga). When the diaphragm itself
is completely relaxed and the actual pressure difference across
the diaphragm is nil, the measured transdiaphragmatic pressure has a minimum value, usually approximately 10 cm H2O,
which is attributed mostly to the gravitational hydrostatic difference between esophageal and gastric pressures. This hydrostatic
transdiaphragmatic pressure, which changes only
Am J Respir Crit Care Med Vol 165. pp 580587, 2002
slightly
with breathing (3), is usually subtracted from reported
DOI: 10.1164/rccm.AT0602
Internet address: www.atsjournals.org
measurements
of Pdi.
Pressure differences across viscoelastic, plastoelastic structures such as the lungs and chest wall depend on the structures volume, volume history, and rate of change of volume.
Accordingly, pressure differences across respiratory structures
are often represented as characteristic pressurevolume (PV)
curves (4). For the relaxed respiratory system, transpulmonary, transthoracic, and transrespiratory pressures are usually
plotted against lung volume in a Rahn diagram (Figure 1). The
PV characteristics shown in Figure 1 are of a relaxed subject
slowly inflated or deflated by a pressure source at the airway
opening. All the passive structures show an increase in volume
with an increase in the pressure difference across them. When
two pneumatic structures are in series, for example, the lung
and the chest wall, the pressure difference across both structures (the transrespiratory pressure) is the sum of the pressure
differences across each, and the volume displacements of the
whole are equal to the volume displacements of each part. The
PV curve can be locally described by the volume at a given
pressure and the slope (compliance) at that point. The compliance of a passive structure at a given volume is the ratio of volume change to pressure change (i.e., the slope of the characteristic PV curve at that volume).
Methodology
581
The Rahn diagram is useful for describing the elastic properties of passive systems. Each curve reflects the pressure difference developed by this structure for a range of volumes. Static
compliance determined from these curves can be used for diagnosis. For example, the compliance of the lung is decreased
in interstitial lung disease and increased in emphysema. Chest
wall compliance is decreased in ankylosing spondylitis and
obesity.
Disadvantages
582
Figure 2. Campbell diagram. Graphical analysis of the work done during a breathing cycle by the inspiratory muscles. Vertical hatching:
Work done to overcome flow resistance of the lungs. Horizontal hatching: Work done to overcome elastance of the lungs and chest wall.
Modified by permission from Macklem PT, Mead J, editors. Handbook
of physiology. Vol. 3: The respiratory system, Part 3. Bethesda, MD:
American Physiological Society; 1986. p. 495.
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Equipment
Measurements of pressure and volume are described in Sections 1 and 2 of this Statement.
Applications
Scientific Basis
The following properties of the chest wall and lung are found
by analysis of Campbell diagrams:
583
Another device that has gained acceptance since its introduction more than 15 years ago is the respiratory inductive
plethysmograph (RIP), which uses two elastic bands that surround the rib cage and abdomen to provide a signal that varies
with cross-sectional area. The RIP can measure ventilation
within about 5% compared with the spirometer, and can reveal the relative contributions of rib cage and abdomen to
breathing. This device is widely used to monitor ventilation.
The first device to be used routinely for quantitative measurements of chest wall displacements was the respiratory magnetometer (11), which uses pairs of small electromagnetic coils
fixed to the skin to measure anteroposterior or other diameters of rib cage or abdomen.
Advantages. These electronic calipers are precise, accurate, and consistent, allowing repeated measurements in an individual over many days (12). Also, because they measure diameters (intercoil distance), they are useful for documenting
distortions of the chest wall shape as during asthma attacks
(13) or forceful respiratory efforts (14). They are also useful
for measuring ventilation at rest.
584
Advantages. The RIP is easy to use. Because the belts encircle a large part of the rib cage and abdomen, integumental
mobility and cross-sectional shape distortions are less problematic than with magnetometers, and therefore the RIP is often
used during sleep or exercise. The RIP is more accurate than
magnetometers in estimating lung volume change (15), perhaps
because its signal varies with cross-sectional area and samples a
larger part of the moving chest wall than do magnetometers.
Disadvantages. The RIP measures changes relative to an unknown baseline, and its accuracy depends on lung volume calibration at the time of study (see below). In addition, movement
of the belts or changing body position can affect calibration.
Calibration of RIP and magnetometers. Numerous methods
for calibrating the magnetometer and RIP signals for estimating lung volume displacement have been described. All methods determine coefficients for rib cage and abdominal signals,
and most require simultaneous spirometric measurements of
lung volume change during periods of breathing in which the
contributions of rib cage and abdomen to tidal volume vary. In
the method described by Konno and Mead (Figure 4), the volumemotion coefficients of rib cage and abdomen are established by having subjects perform an isovolume maneuver at
two volumes that differ by a known amount. Volume calibration is accomplished by extending the isovolume lines to the
axes, where they indicate the known volume difference. Calibration can also be accomplished by using statistical techniques based on tidal breathing without isovolume maneuvers,
and semiautomated procedures and computer programs incorporated into some commercial devices can simplify calibration in practice. Alternatively, one can assume a standard ratio of the volumemotion coefficients of rib cage and abdomen
instead of finding the ratio experimentally, and calibrating the
combined signal with a spirometer (16). The use of a standard
gain ratio when measuring tidal volume is probably as accurate as more elaborate methods of calibration and, importantly, avoids extreme errors in calibration that can occur with
untrained subjects. We recommend use of standard ratios for
measuring tidal volume, especially in untrained subjects.
Methodology: Respiratory Area Flux Meter
Another device, the respiratory area flux meter, also uses expandable coils that surround the rib cage and abdomen, but in
this case the subject must also lie within large fixed-field coils
mounted in a frame (17).
Advantages. The principal advantage of the area flux meter
is that it measures the cross-sectional areas of the rib cage and
abdomen accurately.
Disadvantages. Although promising, this technique has not
yet been widely applied. The necessity for large field coils may
relegate this device to research applications.
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2002
Disadvantages
Chest wall motion is easy to measure and provides information about respiratory muscle activity.
Disadvantages
585
Decramer and Macklem introduced a method for inferring respiratory muscle action by measuring esophageal and gastric
pressures (23) For example, inhalations made with rib cage
muscles alone (as in diaphragm paralysis) result in decreases
in both esophageal pressure, which is normal, and in gastric
pressure, which is not, whereas diaphragmatic inhalations result in increased gastric pressure and a negative swing in Pes
(lung inflation) (Figure 5).
Advantages
Using chest wall pressures by themselves to infer muscle actions leaves some uncertainty, as does the use of displacements
already described here. Macklems method of analysis assumes that abdominal muscles are relaxed. When they are not,
pressure changes are ambiguous and difficult to interpret.
Nevertheless, this remains an interesting research tool and has
potential for development.
tends to displace the abdominal wall inward and increase abdominal pressure. Therefore, a movement down and to the
right of the relaxation line in Figure 6 reliably indicates abdominal muscle contraction. Similarly, diaphragm contraction
(or paralysis) can be inferred from deviations of the diaphragms PV data in relation to its relaxation characteristic. If
the diaphragm shortens or remains relatively isometric and
transdiaphragmatic pressure increases, the diaphragm must be
actively contracting. For examples of the use of such plots, see
Goldman and coworkers (25) and Mead and coworkers (26).
The rib cage presents a challenge in pressurevolume analysis because no single pressure difference characterizes the
pressures acting on the whole structure. The internal pressure
applied to the lung-apposed surface of the rib cage can be
characterized by pleural (esophageal) pressure, but pressure
in the caudal rib cage apposed to abdominal viscera and diaphragm (the zone of apposition) is closer to abdominal (gastric) pressure than pleural pressure. In addition, the diaphragm itself can have an inspiratory effect on the lower rib
cage when it contracts. Therefore, the pressure acting on or
contributed by the rib cage is generally neither pleural nor abdominal pressure but some combination of the two (27). This
complication can be handled by more elaborate analysis of
chest wall motion and pressures (28).
Advantages
586
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2002
Advantages
CONCLUSION
This Section of the Statement has considered the mechanical
properties and function of the chest wall, assessed by volume
Figure 6. Abdominal displacement (Vab) gastric pressure (Pga) characteristic during relaxation and contraction of abdominal muscles.
587
13.
14.
15.
16.
17.
18.
19.
20.
21.
22.
23.
24.
25.
26.
27.
28.
29.
30.
31.
32.
33.
34.
and chest wall compliance and dimensional changes during respiratory maneuvers. Am Rev Respir Dis 1989;139:615620.
Ringel ER, Loring SH, McFadden ER Jr, Ingram RH Jr. Chest wall configurational changes before and during acute obstructive episodes in
asthma. Am Rev Respir Dis 1983;128:607610.
McCool FD, Loring SH, Mead J. Rib cage distortion during voluntary
and involuntary breathing acts. J Appl Physiol 1985;58:17031712.
Banzett RB, Mahan ST, Garner DM, Brughera A, Loring SH. A simple
and reliable method to calibrate respiratory magnetometers and Respitrace. J Appl Physiol 1995;79:21692176.
Estenne M, De Troyer A. Relationship between respiratory muscle electromyogram and rib cage motion in tetraplegia. Am Rev Respir Dis
1985;132:5359.
Sartene R, Martinot-Lagarde P, Mathieu M, Vincent A, Goldman M,
Durand G. Respiratory cross-sectional areaflux measurements of the
human chest wall. J Appl Physiol 1990;68:16051614.
Cala SJ, Kenyon CM, Ferrigno G, Carnevali P, Pedoti A, Macklem PT,
Rochester DF. Chest wall and lung volume estimation by optical reflectance motion analysis. J Appl Physiol 1996;81:26802689.
Cohen CA, Zagelbaum G, Gross D, Roussos C, Macklem PT. Clinical
manifestations of inspiratory muscle fatigue. Am J Med 1982;73:308316.
Mead J, Loring SH. Analysis of volume displacement and length changes of
the diaphragm during breathing. J Appl Physiol 1982;53: 750755.
Loring SH, Mead J, Griscom NT. Dependence of diaphragmatic length
on lung volume and thoracoabdominal configuration. J Appl Physiol
1985;59:19611970.
Loh L, Goldman M, Newson Davis J. The assessment of diaphragmatic
function. Medicine (Baltimore) 1977;56:165169.
Decramer M, Macklem PT. Pressures developed by the respiratory muscles. In: Roussos C, editor. The thorax. Part B: Applied physiology.
New York: Marcel Dekker; 1995. p. 10991126.
Konno K, Mead J. Static volumepressure characteristics of the rib cage
and abdomen. J Appl Physiol 1968;24:544548.
Goldman MD, Grimby G, Mead J. Mechanical work of breathing derived from rib cage and abdominal VP partitioning. J Appl Physiol
1976;41:752763.
Mead J, Smith JC, Loring SH. Volume displacements of the chest wall
and their mechanical significance. In: Lenfant C, editor. The thorax.
Vol. 85: Lung biology in health and disease. New York: Marcel Dekker; 1995. p. 565586.
Loring SH, Mead J. Action of the diaphragm on the rib cage inferred
from a forcebalance analysis. J Appl Physiol 1982;53:756760.
Grassino A, Goldman MD, Mead J, Sears TA. Mechanics of the human
diaphragm during voluntary contraction: statics. J Appl Physiol 1978;
44:829839.
De Troyer A. The respiratory muscles. In: Cristal R, West J, Weibel E,
Barnes P, editors. The lung: scientific foundations, 2nd ed. Philadelphia, PA: Lippincott-Raven; 1997. p. 12031214.
Lopata M, Evanich MJ, Lorenco R. Quantification of diaphragm EMG
to CO2 rebreathing in humans. J Appl Physiol 1997;43:262270.
Brancatisano A, Engel LA, Loring SH. Lung volume and effectiveness
of inspiratory muscles. J Appl Physiol 1993;74:688694.
Schweitzer TW, Fitzgerald JW, Bowden A, Lynn-Davies P. Spectral analyses
of human diaphragm electromyogram. J Appl Physiol 1979; 46:152165.
Sinderby C, Lindstrom L, Grassino A. Automatic assessment of EMG
quality. J Appl Physiol 1995;79:18031815.
Sinderby C, Beck J, Spahija A, Weinberg J, Grassino A. Voluntary activation of the human diaphragm in health and disease. J Appl Physiol
1998;85:21462158.
TRANSMISSION RADIOGRAPHY
Radiography remains the most used technique for evaluating
the position and movement of the diaphragm. Postero-anterior (P-A) and lateral views of the thorax at total lung capacity
can be supplemented by radiographs at other static lung volumes and movement of the hemidiaphragms as assessed by
fluoroscopy.
Limitations
quired enlargement of total lung capacity, as in severe emphysema, the domes are lower (the level of the right dome at the
anterior end of the seventh rib or lower) with flattening and a
larger radius of curvature, visible on both P-A and lateral radiographs. If a line is drawn on a P-A radiograph from the vertebrophrenic angle to the costophrenic angle, the maximum
curvature of the dome, assessed at 90 to this line, should normally be at least 1.5 cm. In the most severe disease the domes
may be flat or even inverted with loss of the zone of apposition, allowing visualization on the P-A radiograph of the insertions of the diaphragm into the lower ribs.
Excursion of hemidiaphragm domes during tidal breathing. High-speed cassette changers or video fluoroscopy can
provide dynamic information. In a study of inspiratoryexpiratory radiographs obtained during quiet tidal breathing in the
erect position from 350 subjects, 3080 years of age, and without evidence of respiratory disease, the mean tidal excursions
of the domes of the right and left hemidiaphragms were found
to be 3.3 and 3.5 cm, respectively (6). Tidal diaphragmatic
movement averaged 0.5 cm less in women than in men. Despite similar mean values, unequal movement of the two hemidiaphragmatic domes in an individual subject is common,
most commonly being greater on the right (5).
In bilateral diaphragm paralysis individuals may breathe by
active expiration below relaxation volume followed by passive
inhalation, during which the diaphragm may descend, at least
during early inspiration, leading to erroneous conclusions
about diaphragm function (6, 7). Because relaxation volume
decreases in the supine position, subjects are less likely to be
able to breathe by active expiration below the relaxation volume and passive descent of diaphragm during inspiration is
less likely to occur.
Unilateral diaphragm paralysis is easier to detect because
there is paradoxic motion during tidal inspiration, with ascent
of the paralyzed dome, contrasting with descent of the normal
hemidiaphragm; this contrast can be amplified by the sniff
test, which induces a vigorous, short-lived contraction in the
normal hemidiaphragm. Because of normal variations in movement of the two diaphragms, relative weakness of one hemidiaphragm (such as after cardiothoracic surgery) is difficult to
detect radiographically.
Estimates of Change in Diaphragm Length from Radiographs
at Different Lung Volumes
Figure 1. Three-dimensional reconstruction, using spiral computed tomography, of diaphragm contour at supine functional residual capacity in a normal subject (A) and a patient with hyperinflation due to
chronic obstructive pulmonary disease (B). The silhouette of the domes
projected on a transmission radiograph may arise from different planes.
Scale in centimeters. Reprinted by permission from Reference 3.
allows for inspiratory expansion of the lower rib cage but neglects change in shape of the domes (9). Radiographic changes
in diaphragm length over the vital capacity have been estimated in patients with chronic obstructive pulmonary disease
(1012). Nonradiographic methods can be used to measure the
internal diameter of the rib cage (calipers or magnetometers,
with chest wall thickness measured by ultrasound) and the
length of the zone of apposition (ultrasound; see below); the
accuracy of estimates of change in the diaphragm length by
nonradiographic methods therefore will be influenced by
whether the dome shape remains reasonably constant (or its
change can be predicted) over the vital capacity (11, 12).
ULTRASOUND
Diaphragm
Dome movement. Ultrasound has been used to monitor displacement of the dome of the diaphragm during respiratory
maneuvers, with craniocaudal excursions of the posterior dome
measured either with a transducer on the lateral chest wall
(15) or with a probe placed on the upper abdomen and directed toward the dome (16, 17). Visualization of the right
589
Figure 2. B-mode ultrasonogram of the normal diaphragm in the zone of apposition (between the two
arrows) visualized through
a lower right intercostal space.
Scale division on x and y axis
is 10 mm. Reprinted by permission from Reference 14.
590
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TABLE 1. RADIOGRAPHY
Name of Test
Information Provided
Diagnostic Purposes
Set of radiographs at
different lung inflation
between RV and TLC
Unilateral/bilateral diaphragm
paralysis
Emphysema
Unilateral or bilateral diaphragm
paralysis
How to Perform
Standard radiographic techniques
Fluoroscopy or rapid-cassette
change radiography
Definition of abbreviations: P-A postero-anterior; RV residual volume; TLC total lung capacity.
TABLE 2. ULTRASOUND
Name of Test
Information Provided
Diagnostic Purposes
How to Perform
Diaphragm
Dome ultrasound
Thickening during
respiratory maneuvers
Placement of intramuscular
electrodes
High-resolution probe
(7.5 MHz) over appropriate
muscles. B-mode
VOLUMETRIC IMAGING
Volumetric computed tomography scans (2, 3, 3739) and
magnetic resonance imaging (1, 40, 41) can determine the configuration of the thoracic cavity. Both methods can be used to
determine the detailed shape of the diaphragm (Figure 1), the
rib cage, and ribs in normal (1, 2, 38, 39) and emphysematous
(3, 4244) subjects. Such data have been used with engineering analysis to determine the distribution of tension in the canine diaphragm from measurements of transdiaphragmatic
pressure (37). To date, use of these methods has been limited
to research and few measurements of diaphragm thickness
have been made. Clinical use of both imaging methods is still
limited by the expense of data acquisition and the laborious
data analysis. Computed tomography scans are complicated
by radiation exposure and magnetic resonance imaging is
complicated by prolonged data acquisition times, which must
assemble average data over numerous breaths; both can be applied only in horizontal postures.
NUCLEAR MEDICINE
Both single-photon emission computed tomography (SPECT)
and positron emission tomography (PET) scans provide volumetric information, which can be used to identify the surface
of ventilated or perfused lungs. Because the outer surface of
the lung is apposed to the rib cage and diaphragm, the configuration of the diaphragm and rib cage can also be determined
by these methods. Both techniques offer poor spatial and temporal resolution and there are no published data in which they
have been used to analyze respiratory muscle function.
SUMMARY
Radiographic techniques are widely used to assess respiratory
muscle function (summarized in Table 1). Ultrasound is increasingly used, particularly to assess the diaphragm (Table
2). Volumetric imaging (computed tomography and magnetic
resonance imaging) has limited research application.
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15. Houston JG, Morris AD, Howie CA, Reid JL, McMillan N. Technical
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changes in the zone of apposition and diaphragm length during maximal respiratory efforts. Thorax 1994;49:634638.
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thickness and inspiratory strength in patients with Duchenne muscular dystrophy. Thorax 1997;52:472475.
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the supine and prone position on diaphragm thickness in healthy term
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27. McCool FD, Conomos P, Benditt JO, Cohn D, Sherman CB, Hoppin FG
Jr. Maximal inspiratory pressures and dimensions of the diaphragm.
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28. Gottesman E, McCool FD. Ultrasound evaluation of the paralyzed diaphragm. Am J Respir Crit Care Med 1997;155:15701574.
29. Wait JL, Johnson RL. Patterns of shortening and thickening of the human diaphragm. J Appl Physiol 1997;83:11231132.
30. Zifko U, Hartmann M, Girsch W, Zoder G, Rokitansky A, Grisold W,
Lischka A. Diaphragmatic paresis in newborns due to phrenic nerve
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of stress in the canine diaphragm. J Appl Physiol 1994;76:20702075.
38. Krayer S, Rehder K, Vettermann J, Didier EP, Ritman EL. Position and
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ELECTROMYOGRAPHY
Rationale
The upper airway serves as a common conduit of the respiratory, digestive, and phonatory systems. Whereas respiration requires patency of the upper airway throughout the respiratory
cycle, swallowing and phonation are dependent on upper airway closure. During swallowing, upper airway muscles close the
velopharyngeal sphincter and create a peristaltic-like constriction of the collapsible pharyngeal airway to propel the food bolus into the esophagus. Activation of upper airway muscles during phonation constricts valvelike structures at the velopharynx
and glottis. To maintain airway patency during respiration, activation of upper airway muscles during inspiration dilates and
stiffens the airway. Loss of upper airway muscle activity during
sleep is felt to predispose to pharyngeal airway closure in patients with OSA (Figure 3). Electromyography has been used
extensively in research studies to determine the respiratory-related activation of upper airway muscles and their role in the
pathogenesis of OSA. In particular, information on time domains, coordination among muscles, and relative amounts of
activity (integration) represents the parameters often used (see
ELECTROMYOGRAPHY in Section 3 of this Statement).
Methodology
Advantages
Equipment
594
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cles, and genioglossus activity may not always be representative of motor output to other upper airway or even pharyngeal
muscles. For example, during quiet breathing, the pharyngeal
constrictors rarely exhibit respiratory-related activity, whereas
the posterior cricoarytenoid, a vocal cord abductor, uniformly
exhibits phasic inspiratory activity, and the thyroarytenoid, a
vocal cord adductor, exhibits phasic expiratory activity (7, 13, 21).
Disadvantages
Applications
Figure 1. Some muscles that influence the pharyngeal airway. Contraction of muscles attaching to the hyoid bone can displace the anterior pharyngeal wall ventrally, helping to increase airway size. Muscles
attached to the soft palate help regulate the route of breathing.
595
Figure 3. Electromyogram (EMG) of the genioglossus (GG) muscle during two obstructive apneas
(OSAs) in nonrapid eye movement sleep. Airway
closure (horizontal lines) is associated with a decrease in GG activation. GG activation progressively increases during the obstructive, apneas but
airway reopening, as evidenced by the resumption
of tracheal breathing sounds, does not occur until there is a large burst of GG activity. The time
constant of the oxygen saturation signal delays
the appearance of the oxygen saturation nadir
until after airway reopening. EEG electroencephalogram; SaO2 arterial oxygen saturation.
used equation is: P KV2 (Equation 2). Changes in upper airway resistance can be assessed indirectly by measuring total
pulmonary resistance with the passage of an esophageal balloon. This method is valid if resistance across the lower airways remains constant. Therefore, these measurements must
be obtained at a given lung volume.
The measurement of upper airway resistance requires two
pressure transducers to measure the pressure drop across the
airway and a pneumotachograph connected to a differential
pressure transducer for the measurement of flow. Pressure is
calibrated in cm H2O and flow in L second1. As the measurements are obtained under dynamic conditions, the three
signals should remain in phase up to a frequency of 10 Hz.
Advantages
When properly controlled, measurements of upper airway resistance can provide a global assessment of the effect of changes
in upper airway muscle activity on upper airway function.
596
Disadvantages
FIBEROPTIC IMAGING
Upper airway resistance is only an indirect measurement of upper airway muscle activity. Measurements must be carefully controlled as upper airway resistance can be affected by many other
factors (see previous sections). Measurement of upper airway resistance requires an invasive procedure that is of low morbidity.
Rationale
Applications
The determination of upper airway resistance is a clinical research technique that has been used to assess the effect of changes
in chemical drive and sleepwakefulness states on upper airway size and muscle activity. Nasal rhinometry, the measurement of nasal airway resistance, is used by ear, nose, and throat
physicians to assess the patency of the nasal passages.
INDIRECT LARYNGOSCOPY
Rationale
Indirect laryngoscopy is performed in the awake patient by advancing a small angled mirror through the open mouth to the
soft palate while protruding the subjects tongue. Illumination of
the angled reflecting surface allows visualization of the glottic aperture through the oral cavity. Topical anesthesia of the soft palate can help minimize the gag reflex. As the cords are being visualized, the patient is instructed to vocalize an e sound that
normally adducts the vocal cords. Failure of one cord to adduct
indicates ipsilateral vocal cord paralysis. In the case of bilateral
vocal cord paralysis, both cords are close to the midline and show
no abduction during inspiration and may even show paradoxical
movement with respiration due to the effects of changes in intralumenal pressure on inspiration and expiration. Direct laryngoscopy is performed under general anesthesia. With the advent
of fiberoptic scopes, this latter technique is rarely indicated in
adults to assess the presence or absence of vocal cord paralysis.
Advantages
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2002
Fiberoptic imaging is an invasive procedure that provides direct visualization of the upper airway. However, it is easily
performed in the awake adult patient and is associated with
very little discomfort. After topical anesthesia of one nasal
passage, the fiberoptic scope is advanced through the nares
and along the floor of the nasal passage into the pharyngeal
airway. Depending on the outer diameter of the scope, prior
application of a nasal decongestant may be of benefit. The
glottic aperture is easily visualized from the hypopharynx. No
attempt should be made to touch or pass through the unanesthetized glottis during this visual examination.
Equipment
Application as a diagnostic technique requires a fiberoptic nasopharyngoscope, optimally with an outer diameter of 4 mm or
less, attached to a light source. Physicians performing the procedure should be specially trained in this technique.
When using fiberoptic imaging as a research technique to
quantify changes in upper airway dimensions, it is necessary to
have a camera attached to the fiberoptic scope to obtain videotape recordings. Individual frames of the videotape can
then be analyzed offline, ideally with a personal computer
frame grabber and digitizing software. Methods have been described to calibrate the measurements in metric units (36, 37).
Advantages
The fiberoptic equipment is expensive. Standardized techniques should be instituted to sterilize the scope between procedures. Passage of the fiberoptic scope may be associated
with a vasovagal reaction associated with hypotension and loss
of consciousness. Adequate supportive care should be available in the event of this complication.
Use of fiberoptic imaging of the upper airway in clinical research is laborious even with computer-assisted analysis. In
addition to difficulties with calibration of measurements in
metric units, the lack of depth perception on the videotape images makes it particularly difficult to detect the edge of the
pharyngeal airway that should be measured. Movement and
clouding of the scope are other technical difficulties frequently encountered during research studies.
Disadvantages
As a visual assessment of intrinsic laryngeal muscle activity, indirect laryngoscopy is limited to determining the presence or absence of motor innervation. Bilateral but asymmetrical movement
of the vocal cords is difficult to quantify. This finding may suggest
vocal cord paresis but can also arise from other conditions.
597
Routine CT scanners are used (see Section 7 of this Statement). Three-dimensional reconstruction may be helpful.
Advantages
Advantages
Acoustic reflection is noninvasive, nonirradiating, inexpensive, compact, and can be performed rapidly. It can be used in
large numbers of subjects in a variety of different body postures (46).
Disadvantages
Acoustic reflection cannot be used to visualize the retropalatal airway and cannot be used during sleep.
Applications
Acoustic reflection is applicable to population or physiological studies of upper airway size. It is of little value to individual patients.
Applications
FLOWVOLUME LOOPS
Rationale
Flowvolume loops have the potential to be used to detect upper airway obstruction during wakefulness as a predictor of
airway occlusion during sleep.
Equipment
Recording of flowvolume loops requires a body plethysmograph, rapid response spirometer, or pneumotachograph (see
Section 1 of this Statement).
Advantages
Equipment
Disadvantages
Advantages
ACOUSTIC REFLECTION
Rationale
Applications
POLYSOMNOGRAPHY
Rationale
Polysomnography is the study of several physiological variables during sleep, including the recording of sleep itself. The
precise items recorded will vary but usually include electroencephalography, electro-oculography, electromyography, respiratory pattern, snoring, oxygen saturation, transcutaneous carbon dioxide tension, electrocardiography, and body posture
(4951). This allows the recognition of events that occur during sleep and offers the advantage over other techniques that
sleep can be identified with certainty.
In patients with marked respiratory muscle weakness, detection of respiratory movement during obstructive events from
external sensors may be very difficult or impossible. Indeed,
true obstructive events may be scored even by skilled observers
as central. There are three ways around this problem. First,
esophageal pressure may be recorded during polysomnography in all such patients (52, 53). Second, flattening of the flow
time curve during these events in sleeping subjects may be
helpful (54). Third, some centers have adopted the approach
that patients with multiple central apneas should be treated
with continuous positive airway pressure to determine whether
these events respond to continuous positive airway pressure.
598
Equipment
Applications
Computerized systems are generally used, which allows the recording of the all-night data on to optical or compact disk formats. Detection of fluctuation in nasal pressure during inspiration and expiration reflects changes in inspiratory and expiratory
airflow and therefore is a promising method for the detection
of hypopneas (50, 55). Studies have shown that nasal pressure
is more sensitive than thermal sensors for detecting hypopneas and that the square root of the pressure signal improves
the estimate of airflow (56, 57).
Advantages
Polysomnography is a valuable method of identifying sleeprelated hypoventilation in patients with respiratory muscle
problems and whether they have related sleep apneahypopnea syndrome as well. It is useful in some patients to monitor
progress on treatment, such as noninvasive positive pressure
ventilation.
MUSCLE BIOPSY
Rationale
VOL 166
2002
CONCLUSION
Disadvantages
References
Technique
The tongue is the only upper airway muscle for which force
can be measured.
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30. Anch AM, Remmers JE, Bunce H III. Supraglottic airway resistance in
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31. Wasicko MJ, Hutt DA, Parisi RA, Neubauer JA, Mezrich R, Edelman
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32. White DP, Lombard RM, Cadieux RJ, Zwillich CW. Pharyngeal resistance in normal humans: influence of gender, age, and obesity. J Appl
Physiol 1985;58:365371.
33. Hudgel DW, Martin RJ, Johnson B, Hill P. Mechanics of the respiratory
system and breathing pattern during sleep in normal humans. J Appl
Physiol 1984;56:133137.
34. Kuna ST, Vanoye CR, Griffin JR, Updegrove JD. Effect of hypercapnia
on laryngeal airway resistance in normal adult humans. J Appl Physiol
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35. Isono S, Morrison DL, Launois SH, Feroah TR, Whitelaw WA, Remmers JE. Static mechanics of the velopharynx of patients with obstructive sleep apnea. J Appl Physiol 1993;75:148154.
36. Morrison DL, Launois SH, Isono S, Feroah TR, Whitelaw WA, Remmers JE. Pharyngeal narrowing and closing pressures in patients with
obstructive sleep apnea. Am Rev Respir Dis 1993;148:606611.
37. Kuna ST, Vanoye CR. Laryngeal response during forced vital capacity
maneuvers in normal adult humans. Am J Respir Crit Care Med 1994;
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38. Haponik EF, Smith PL, Bohlman ME, Allen RP, Goldman SM, Bleecker
ER. Computerized tomography in obstructive sleep apnea: correlation
of airway size with physiology during sleep and wakefulness. Am Rev
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39. Shepard JW, Thawley SE. Evaluation of the upper airway by computerized tomography in patients undergoing uvulopalatopharyngoplasty
for obstructive sleep apnea. Am Rev Respir Dis 1989;140:711716.
40. Rodenstein DO, Dooms G, Thomas Y, Liistro G, Stanescu DC, Culee C,
Aubert-Tulkens G. Pharyngeal shape and dimension in healthy subjects, snorers and patients with obstructive sleep apnoea. Thorax 1990;
45:722727.
41. Horner RL, Mohiaddin RH, Lowell DG, Shea SA, Burman ED, Longmore DB, Guz A. Sites and sizes of fat deposits around the pharynx in
obese patients with obstructive sleep apnoea and weight matched controls. Eur Respir J 1989;2:613622.
42. Shelton KE, Gay SB, Hollowell DE, Woodson H, Suratt PM. Mandibular enclosure of upper airway and weight in obstructive sleep apnea.
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43. Shelton KE, Woodson H, Gay S, Suratt PM. Pharyngeal fat in obstructive sleep apnea. Am Rev Respir Dis 1993;148:462466
44. Fredberg JJ, Wohl MB, Glass GM, Dorkin HL. Airway area by acoustic
reflections measured at the mouth. J Appl Physiol 1980;48:749758.
45. Bradley TD, Brown IG, Grossman RF, Zarnel N, Martinez D, Phillipson
EA, Hoffstein V. Pharyngeal size in snorers, nonsnorers, and patients
with obstructive sleep apnea. N Engl J Med 1986;315:13271331.
46. Martin SE, Marshall I, Douglas NJ. The effect of posture on airway calibre in patients with the sleep apnea/hypopnea syndrome. Am J Respir
Crit Care Med 1995;152:721724.
47. Riley R, Guilleminault C, Herran J, Powell N. Cephalometric analyses
and flow volume loops in obstructive sleep apnea patients. Sleep 1983;
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48. Krieger J, Weitzenblum E, Vandevenne A, Stierle J, Kurtz D. Flow volume curve abnormalities and obstructive sleep apnea syndrome. Chest
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49. Douglas NJ, Thomas S, Jan MA. Clinical value of polysomnography.
Lancet 1992;339:347350.
50. American Academy of Sleep Medicine Task Force. Sleep-related breathing disorders in adults: recommendations for syndrome definitions and
measurement techniques in clinical research. Sleep 1999;22:667689.
51. American Sleep Disorders Association. Practice parameters for the indications for polysomnography and related procedures. American Sleep
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52. Tvinnereim M, Mataeika S, Cole P, Height J, Hoffstein V. Diagnosis of
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600
56.
57.
58.
59.
60.
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61. Shepard JW Jr, Thawley SE. Localization of upper airway collapse during sleep in patients with obstructive sleep apnea. Am Rev Respir Dis
1990;141:13501355.
62. Hudgel DW, Harasick T, Katz RL, Witt WJ, Abelson TI. Uvulopalatopharyngoplasty in obstructive sleep apnea: value of preoperative localization of site of upper airways narrowing during sleep. Am
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63. Launois SH, Feroah TR, Campbell WN, Issa FG, Morrison D, Whitelaw
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602
VOL 166
2002
603
Reference
No.
32
33
ml/cm H2O
ml/cm H2O/kg
Preterm
Infancy
5.7 1.4
17.4 6.7
(310)
(25)
2.8 0.87
(13)
2.0 0.51
13
Sharp
Mittman
37
38
Ccw
Age Range
(yr)
516
5
8
12
16
Adulthood
2029
3039
4049
5059
6069
7079
20.1 7.7
78
106
156
184
4
4
4
3
350
250
250
250
136
210
5
3.5
3.5
3.5
2
3
Ccw/CL
(36)
(12)
(12)
net muscle force, i.e., the product of pressure and surface area
over which the pressure is applied (13).
Clinical application. Measurements of PI,max and PE,max
are useful in children and/or adolescents with neuromuscular
disorders (4850), with cystic fibrosis (5155), and with chronic
obstructive pulmonary disease (16). In the case of hyperinflation, PI,max and PE,max values have to be corrected for the
absolute volume at which measurements were made (16, 53).
PI,max and PE,max measurements may be useful in malnourished children (53). Maximum inspiratory pressure at FRC
provides an assessment of the inspiratory maximal reserve of
the respiratory muscles during quiet breathing in children (16,
55, 56). It has been proposed that inspiratory muscle strength
be assessed by the measurement of the maximal pressure obtained while breathing 5% CO2 at the time of weaning from
MV in infants and children (57).
Nasal Sniff Pressures
Nasal sniff pressure (Pnas,sn) is an established test of inspiratory muscle strength in adults (see Section 2 of this Statement).
The technique has been applied to children, normal values
have been reported (58), and this simple noninvasive measure
has considerable promise in pediatric practice.
Crying Pressures: Crying PI,max and PE,max
2
1.2
1
0.8
0.7
0.7
Rationale. Crying transdiaphragmatic pressure (Pdi) measurements allow assessment of diaphragm muscle strength during
inspiratory crying efforts in infants.
Measurements. Accurate recordings of Pes and gastric pressure (Pga) are essential.
Advantages. Transdiaphragmatic pressure is specific for diaphragmatic contraction.
Disadvantages. Disadvantages include (1) the fact that reliability of Pdi requires accurate measurements of Pes; and (2)
similar limitations to crying PI,max with respect to variability
in lung volume at which Pdi is measured during crying efforts.
604
Reference
Age
(yr)
At FRC
At FRC
Males
47
13
47
13
47
13
41*
46
47
42
41
8
77 24
70 24
105 27
97 22
114 27
130 16
111 34
105 23
10
1113
1317
107 26
126 22
79
99 23
90
123 27
90101
161 37
176 24
131 30
107129
114 35
166 44
83 16
100 23
132 33
8
71 29
59 21
71 29
59 21
108 29
112 20
85 28
98 25
10
1113
1317
76 25
109 21
62
74 25
90
74 25
7786
126 32
138 31
95 29
86107
86 22
135 29
2002
tion of sleep state. There is a relatively high CV, 11.7% in children (15); variability has not been determined in infants.
Normal values. Occlusion pressure was found to be 4.4 cm
H2O in full-term newborns (61, 62) and 3.6 cm H2O in preterm
infants (62). Occlusion pressures are available in awake children from 416 years of age during resting breathing of room
air (Table 3) (15). Pmo,0.1 decreases as a power function with
age and reaches adult values at approximately 13 years of age.
Clinical application. Measurements of Pmo,0.1 are useful
to assess respiratory drive in infants and children with chronic
intrinsic loaded breathing (bronchopulmonary dysplasia [62],
interstitial lung disease [63], chronic obstructive lung disease
[16, 51, 64]).
Inspiratory Pressure Reserve and TensionTime Index
Females
47
13
47
13
47
13
41*
46
47
42
41
VOL 166
65 18
65 18
101 26
605
25.6
14.7
18.9
13.0
0.07
0.09
0.06
costal muscles are inhibited during REM sleep and chest wall
distortion occurs during inspiration. No abdominal muscle activation has been reported in healthy infants nursed in the supine position during NREM sleep (71). Activation of abdominal muscles is observed during NREM sleep while breathing
CO2, but not during REM sleep (71).
Clinical application. The main utility of recording of EMG
of the respiratory muscles is during sleep studies. Persistent
phasic chest wall EMG activity helps to identify obstructive
respiratory events, especially obstructive hypopneas during
sleep, and therefore should limit the use of the invasive measurement of Pes (76). EMG recording of abdominal muscles
assesses the degree of abdominal muscle contraction in children with loaded breathing related to partial upper airway obstruction during sleep (71, 72).
13.9
0.06
Sex
Pmo,0.1*
(cm H2O)
PI
(cm H2O)
PI,max,FRC
(cm H2O)
Male
Female
Male
Female
Male
3.60
3.60
2.80
2.80
2.34
15.2
70
Female
2.34
15.2
59
Male
Female
Male
Female
2.04
2.04
1.82
1.82
14.3
14.3
13.7
13.7
97
77
105
98
Male
Female
Male
Female
1.65
1.65
1.52
1.52
PI/PI,max,FRC
(%)
21.7
10
12
14
16
PTImus
0.10
0.11
Definition of abbreviations: Pmo,0.1 occlusion pressure; PI mean inspiratory pressure; PI,max,FRC maximal inspiratory pressure generated at functional residual capacity; PTImus pressuretime index for all the inspiratory muscles.
* Pmo,0.1 (occlusion pressure) from Gaultier and coworkers (15); Pmo,0.1 is not significantly different between males and females.
TI/Ttot does no change with age in children (15), TTImus was calculated using a T I/
Ttot equal to 0.45, i.e., the mean value obtained in children between 4 and 16 years of
age.
Rationale. The respiratory muscles (diaphragm and intercostals) act on the rib cage to effect respiratory motion and ventilation. Rib cage motion can be taken as an index of intercostal
muscle action, while AB motion can be taken as an index of
diaphragmatic descent. Thus thoracoabdominal motion (TAM)
provides a visual index of respiratory muscle function.
Methods. The most widely used method to assess TAM is respiratory inductive plethysmography, although strain gauges and
magnetometers are also used. Respiratory inductive plethysmography uses thin cloth bands that are placed around the RC
and AB. A wire is sewn into the bands, and when an oscillatory
current is applied, changes in the cross-sectional area of the
chest wall are reflected as changes in the electric inductance of
the wires, displayed as a change in voltage output. Respiratory
inductive plethysmography can be used to quantitate asynchrony by measuring a phase angle, ( 0, synchronous
breathing; 180, paradoxic breathing), between the RC and
AB compartments. The calculation of does not require calibration for volume. Respiratory inductive plethysmography can
also be used to quantitate the relative contribution of the RC
and AB to VT; this does require calibration for volume. Several
techniques have been described for volumetric calibration. The
isovolume, least mean squares, and quantitative diagnostic calibration techniques are described elsewhere (7781) (see DEVICES
USED TO MONITOR BREATHING in Section 6 of this Statement).
Advantages and disadvantages of respiratory inductive plethysmography. Respiratory inductive plethysmography is valuable as a direct, noninvasive measure of chest wall motion and
an indirect measure of respiratory muscle function. Being an
indirect measure, however, chest wall motion can reflect
events other than respiratory muscle function. Chest wall motion is a final common pathway of integrated respiratory system output; it can be influenced by underlying lung mechanics
and Ccw. Thus, asynchronous chest wall motion can represent
neuromuscular weakness (8284), fatigue (85), high Ccw (86),
abnormally low CL or high lung resistance (87, 88), upper airway obstruction (89), effects of anesthesia (90), or a combination of two or more of these. Its major weakness is thus that it
is a nonspecific indicator, and abnormal chest wall motion
must be interpreted in the context in which it occurs.
Calibration of respiratory inductive plethysmography for
volume is difficult in infants, especially in preterm infants with
highly compliant chest walls and paradoxic chest wall motion.
The highly compliant infant chest wall probably invalidates
the assumption of two degrees of freedom (RC and AB) that
is the basis for most respiratory inductive plethysmography
calibration equations. Furthermore, phase angles may be difficult to interpret if breathing does not approximate a sinusoidal pattern (91).
606
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607
Anterior
Middle
Posterior
Mean
97
4
98
2.6
7.4
3.7
4.6
12.1
3.6
9.7
15.2
Infancy
Adulthood
12.
13.
Clinical application. Measurements of upper airway function are useful in assessing children with suspected obstructive
sleep apnea due to abnormalities of either structure or upper
airway muscle activation including those with craniofacial abnormalities, hypertrophied lymphoid tissue, and neuromuscular disease. They can also be useful in cases of vocal cord dysfunction.
14.
15.
16.
17.
CONCLUSION
18.
19.
20.
21.
22.
23.
24.
25.
26.
27.
28.
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88. Allen J, Greenspan J, Deoras K, Keklikian E, Wolfson M, Shaffer T.
Interaction between chest wall and lung mechanics in normal infants
and infants with bronchopulmonary dysplasia. Pediatr Pulmonol
1991;11:3743.
89. Sivan Y, Deakers T, Newth C. Thoracoabdominal asynchrony in acute
upper airway obstruction in small children. Am Rev Respir Dis 1990;
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90. Benameur M, Goldman M, Eccoffey C, Gaultier C. Ventilation and
thoracoabdominal asynchrony during halothane anesthesia in infants. J Appl Physiol 1993;74:15911596.
91. Goldman M, Pagani M, Trang A, Praud J, Sartene R, Gaultier C. Asynchronous chest wall movement during non-rapid eye movement and
rapid eye movement sleep in children with bronchopulmonary dysplasia. Am Rev Respir Dis 1993;147:11751184.
92. Colin A, Hunter J, Stark A, Wohl M. Normal infants and children have
minimal thoraco-abdominal asynchrony assessed by respiratory inductive plethysmography. Am Rev Respir Dis 1993;147:A966.
93. Sackner M, Gonzalez H, Rodriguez M, Belsito A, Sackner D, Grenvik
S. Assessment of asynchronous and paradoxic motion between the
rib cage and abdomen in normal subjects and in patients with chronic
obstructive pulmonary disease. Am Rev Respir Dis 1984;130:588593.
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du diaphragme chez le nourrisson et le jeune enfant. Rev Electroencephalogr Neurophysiol Clin 1983;13:306311.
Similowski T, Fleury B, Launois S, Cathala H, Bouche P, Derenne J-P.
Stimulation magnetique cervicale (SMC). Rev Mal Respir 1988;5:609614.
Rafferty GF, Greenough A, Dimitriou G, Polkey MI, Long A, Davenport
M, Moxham J. Assessment of neonatal diaphragmatic paralysis using
magnetic phrenic nerve stimulation. Pediatr Pulmonol 1999;27:224226
Remmers J, Launois S, Feroah T, Whitelaw W. Mechanics of the pharynx in patients with obstructive sleep apnea. Prog Clin Biol Res 1991;
345:261268.
Smith T, Baska R, Francisco C, McCray G, Kunz S. Sleep apnea syndrome: diagnosis of upper airway obstruction by fluoroscopy. J Pediatr 1978;93:891892.
Schwab R, Gupta K, Gefter W, Metzger L, Hoffman E, Pack A. Upper
airway and soft tissue anatomy in normal subjects and patients with
sleep-disordered breathing: significance of the lateral pharyngeal
walls. Am J Respir Crit Care Med 1995;152:16731689.
Condos R, Norman R, Krishnasamy I, Peduzzi N, Goldring R, Rapoport D. Flow limitation as a noninvasive assessment of residual upper-airway resistance during continuous positive airway pressure
of obstructive sleep apnea. Am J Respir Crit Care Med 1994;150:
475480.
Wilson S, Thach B, Brouillette R, Abu-Osba Y. Upper airway patency
in human infant: influence of airway pressure and posture. J Appl
Physiol 1980;48:500504.
BREATHING PATTERN
Abnormalities in respiratory frequency (fR) and tidal volume
(VT) are extremely common in critically ill patients and, among
other causes, can reflect respiratory muscle dysfunction. In
several studies, an elevated fR has been shown to predict an
adverse outcome in general populations of critically ill patients. In a case-controlled study of patients discharged from
an ICU, fR (p 0.0002) and hematocrit (p 0.01) were the
only continuous variables that predicted readmission to the
ICU (4). Patients readmitted to the ICU had a much higher
mortality than the control patients (42 and 7%, respectively).
In a study of patients who had undergone a cardiopulmonary
arrest, 53% had a documented deterioration in respiratory
function in the 8 hours preceding the arrest (5). Respiratory
frequency was elevated in the majority of these patients
(mean SE, 29 1 breaths/minute), while other routine laboratory tests, including electrocardiograms, showed no consistent abnormalities. These and other studies (6, 7) demonstrate
that tachypnea is an extremely sensitive marker of a worsening clinical status. However, it is also extremely nonspecific,
and a physician needs to undertake additional diagnostic testing to elucidate the nature of the underlying disorder.
Tidal volume (VT), breathing frequency (fR), and minute
ventilation are easy to measure in intubated patients, and the
values are continuously displayed on virtually all modern mechanical ventilators. However, the accuracy and reliability of
the instrumentation used for volume measurements have undergone remarkably little evaluation (8). To ensure reliability
of volume measurements, a simple handheld spirometer is
preferred. Tidal volume is rarely measured in the nonintubated patient, because these patients have a poor tolerance of
mouthpieces. Moreover, such instrumentation usually causes
a spurious increase in VT and decrease in frequency (9, 10).
Systematic studies have not been undertaken in large populations of healthy subjects to define the normal range for
breath components. Moreover, the values depend on whether
recordings are made nonobtrusively or with instrumentation
requiring the use of a mouthpiece (9, 10). The largest study using nonobtrusive methodology in healthy subjects (n 65) reAm J Respir Crit Care Med Vol 165. pp 610623, 2002
vealed
a mean SD VT of 383 91 ml, fR of 16 2.8 breaths/
DOI: 10.1164/rccm.AT10-02
Internet address:
www.atsjournals.org
minute,
and minute
ventilation of 6.01 1.39 L/minute (11).
611
playing asynchronous rib cageabdominal motion had an increased risk of ventilatory failure necessitating mechanical
ventilation (24) and a poor prognosis (24). Subsequently, abdominal paradox and respiratory alternans, i.e., cyclic alteration in the relative contribution of the rib cage and diaphragmatic muscle groups, were thought to reflect respiratory muscle
fatigue (14, 26, 27). Such an interpretation has major implications for the critically ill patient being weaned from mechanical ventilation. Because muscle rest with mechanical ventilation is the main means of reversing fatigue, the presence of
paradox would prohibit the discontinuation of mechanical
ventilation. Patients who fail a weaning trial, as a group, exhibit greater abdominal paradox than successfully weaned patients (28, 29), but there is considerable overlap among individual patients of the two groups. This lack of discrimination
between the two groups of patients partly stems from the fact
that the more seriously ill patients also switch between predominant use of the rib cage and diaphragmatic muscles (14,
28, 29). Moreover, in systematic experimental studies, respiratory muscle fatigue was shown to be neither necessary nor sufficient for the development of abnormal rib cageabdominal
motion (30, 31). Thus, quantification of abdominal paradox
alone is not helpful in detecting respiratory muscle fatigue or
predicting the development of respiratory failure. However,
studies in small numbers of patients suggest that a global measure of overall asynchronous and paradoxic motion of both
the rib cage and abdomen might be useful in predicting ventilatory failure (14, 24, 25, 2830). Because quantification of abnormal rib cageabdominal motion is relatively complex, such an
index cannot be recommended for general clinical use without
undertaking controlled prospective trials to determine if such
a measurement is superior to simpler tests that are more easily
performed (32).
LUNG VOLUMES
Few studies have been conducted in critically ill patients examining the usefulness of lung volume measurements. In a
study of 10 patients with the GuillainBarr syndrome, Chevrolet and Deleamont (33) found that monitoring vital capacity
three times a day was helpful in predicting the need for ventilator support. Five patients required intubation approximately
12 days after the onset of neurological symptoms; vital capacity was 0.82 L (range, 0.651.00 L) immediately before intubation in these patients. In contrast, mean SD vital capacity
was 2.40 0.57 L in another five patients who were managed
without intubation. In general, when vital capacity fell by 50%
Figure 1. A breath-by-breath
plot of respiratory frequency
and tidal volume in a patient
who failed a weaning trial.
The arrow indicates the point
of resuming spontaneous
breathing following discontinuation of ventilator support.
Rapid, shallow breathing developed almost immediately,
suggesting the prompt establishment of a new steady
state. Although it has been
considered that rapid, shallow
breathing may reflect the
presence of respiratory muscle
fatigue, its almost instantaneous development without subsequent
progression is difficult to reconcile with the development of respiratory
muscle fatigue. Reprinted by permission from Reference 13.
from the first recorded value, ventilator support became necessary within the next 36 hours.
Rieder and coworkers (34) examined the accuracy of vital
capacity in predicting the need for mechanical ventilation in
patients with myasthenia gravis. The study consisted of a retrospective chart review of five patients who experienced 10
episodes of acute respiratory failure. Repeated measurements
of vital capacity every 4 hours did not help in predicting the
need for intubation and mechanical ventilation, which was instituted in four of the episodes. Indeed, the lowest values of vital
capacity tended to be found in the patients who did not receive mechanical ventilation, mean SD 11 5 ml/kg, compared with 21 9 ml/kg in the patients who received ventilator support. Although the study population is small, the results
suggest that vital capacity is unlikely to be useful in this disease. The inability to predict deterioration may be due to the
erratic course of this disease, which involves sudden deterioration (see STATIC LUNG VOLUMES in Section 1 and DEVICES USED
TO MONITOR BREATHING in Section 6 of this Statement).
PRESSURE MEASUREMENTS
The respiratory system is an elastic structure that requires the
generation of force (pressure) for its displacement (35). In
many critically ill patients, positive pressure is delivered to the
lungs through an endotracheal tube by a mechanical ventilator
with the aim of improving arterial blood gases and unloading
the respiratory muscles (3638). The total respiratory system
is composed of complex structures, namely the lungs, the upper and lower rib cage, and the diaphragmabdominal compartments, each displaying different mechanical properties; in
disease states, the situation is even more complicated due to
time-constant inhomogeneity, expiratory flow limitation, etc.
(see ASSESSMENT OF THE FUNCTION OF THE ACTIVE CHEST WALL
in Section 6 of this Statement). Nevertheless, assessment of
respiratory system mechanics is commonly based on a relatively simple equation of motion (Equation 1) (35):
(1)
Pappl = 1 C V + RV
where Pappl is the pressure applied to the system by either the
ventilator or the combined action of the ventilator and the pa
tients inspiratory muscles, V and V are the inflation volume
and flow, respectively, C is the respiratory compliance, and R
is the flow resistance. The endotracheal tubes and the ventilator circuits are rather stiff structures, such that a patients
compliance provides a good representation of the overall elastic properties of the patientventilator ensemble. In contrast,
the endotracheal tube poses a substantial, highly flow-dependent resistance, which is important from the standpoint of a
patients respiratory muscle activity, because this resistance
has to be overcome during lung inflation (39, 40) and it may
retard expiratory flows, thus promoting dynamic hyperinflation (41, 42). Due to the flow characteristics of the endotracheal tubes, Equation 1 becomes Equation 2:
2
Pappl = 1 C V + Rt + ( k V + k V )
(2)
1
612
loaded by an amount that should be proportional to the degree of mechanical support (4856). However, in some instances, a patients inspiratory effort during ventilator-assisted
breaths differs only slightly from that during unassisted breathing due to several factors: excessive ventilatory drive consequent to either metabolic factors (e.g., sepsis, fever, etc.) or
psychologic (e.g., pain, anxiety, etc.) phenomena; substantial
time lag between the onset of a patients inspiratory effort and
full machine support due to delayed opening of the ventilator
circuit valves; ventilator-inspiratory flow that does not meet
patient demands, especially at the onset of inspiration; intrinsic positive end-expiratory pressure (PEEP); and excessive VT
that requires a long expiratory time, during which ineffective
patients efforts may occur. If a patients effort remains significant during mechanical ventilation, the respiratory muscles
cannot recover from fatigue. Accordingly, progressive reduction and eventual discontinuation of mechanical ventilation
can be very difficult (2, 3, 57).
Measurement of pressure at the airway opening is easy in
ventilator-dependent patients because a stiff endotracheal tube
bypasses the compliant upper airway, allowing the rapid transmission of changes in alveolar pressure to the airway opening
even in presence of time-constant inhomogeneity (58, 59).
Airway Pressure Contour
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2002
Figure 2. Subtraction of the area subtended by the inflation pressure (Prs)volume (right) or -time (left) curve in
the presence of inspiratory muscle activity (B) from
that recorded during passive inflation (CMV, controlled
mechanical ventilation; A) yields the work of inspiration
performed by the patient (AMV, assisted mechanical
ventilation; shaded area, C) and the pressuretime
product ( P dt) of the inspiratory muscles. Reprinted
by permission from Reference 53.
Recording of changes in pleural pressure (Ppl) represents a basic means of quantifying respiratory muscle activity. Recording
the tidal swings in esophageal pressure (Pes) (as an estimate of
Ppl) and a knowledge of the passive properties of the chest wall
over lung volume allow the quantification of the pressure developed by the muscles, also referred to as muscular pressure
(Pmus). This measurement has facilitated the gathering of important information in the field of mechanical ventilation, both
in quantification of the effort performed by patients receiving
ventilator assistance and for comparison of different modes of
assisted ventilation (see ESOPHAGEAL, GASTRIC, AND TRANSDIAPHRAGMATIC PRESSURES in Section 2 of this Statement).
613
614
The presence of a phase lag between the onset of the decline in inspiratory pressure decay and the time at which the
flow reaches zero indicates the presence of positive alveolar
pressure at end-expiration. Because this positive pressure can
result from either elastic recoil pressure generated by hyperinflation or from activity of abdominal and/or thoracic expiratory muscles, interpretation of this pressure is extremely difficult. Different methods have been proposed to solve this
problem, using the Pdi (94) or the expiratory swings in gastric
pressure (Pga) (95) to estimate the part related to expiratory
muscle activity (see subsequent text). When Pga is not available, one can calculate a range of values between two extremes or bounds: at one extreme, it is assumed that all of the
pressure drop before reaching zero flow is related to dynamic
hyperinflation, and at the other extreme, it is assumed that all
of this pressure drop is related to the relaxation of the expiratory muscles (79).
Measurements of Ppl and derived variables are very helpful in research. In the clinical setting, however, it has gained
relatively little acceptance despite the availability of commercial systems. Some investigators have suggested that Ppl may
help in understanding the reasons for the inability to tolerate
discontinuation from mechanical ventilation (9698). Although
Ppl has potential implications for setting the ventilator, clearcut data are not available on which to base individual targets
for the employment of these measurements. In addition, a
number of artifacts, including interference by cardiac contractions, make automatic calculations unreliable, especially regarding the detection of the end and the onset of both inspiratory and expiratory efforts.
Intrinsic PEEP
In ventilator-dependent patients, end-expiratory alveolar pressure may remain positive even in the absence of external
PEEP whenever the time required to decompress the lungs to
the elastic equilibrium volume is shorter than the expiratory
time (tE) available before the next inspiration (99, 100). This
end-expiratory elastic recoil pressure (Pel,rs) has been termed
occult PEEP, auto PEEP (101), and PEEPi (102). Both abnormalities in a patients respiratory mechanics and inappropriate
ventilator settings may cause PEEPi (100, 101). As in the case
of set PEEP, PEEPi may decrease cardiac output (103, 104),
and by thus impairing respiratory muscle perfusion, contribute
to respiratory muscle dysfunction. Furthermore, PEEPi poses
an inspiratory pressure threshold load during both spontaneous breathing and patient-triggered, assisted modes of mechanical ventilation. Indeed, PEEPi must be fully counterbalanced by the contraction of a patients inspiratory muscles
before the ventilator can be triggered (99), giving Equation 3:
2
Pappl = PEEPi + V C + Rt + ( k 1 V + k 2 V )
(3)
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2002
615
Mechanical work (W) implies that an applied force or pressure (e.g., Pappl in Equation 1) is producing some displacement in a system, e.g., change in volume (V), according to
Equation 4:
w = Pappl V =
Papp V
(4)
Figure 4. Experimental
record illustrating the
method used to determine the level of dynamic
intrinsic PEEP (PEEPi,dyn)
during spontaneous unoccluded breathing efforts in a representative
patient with active expiratory muscles. From
top to bottom, tracings
represent flow ( V), pleural pressure (Ppl), gastric
pressure (Pga), and transdiaphragmatic pressure
(Pdi). The first vertical line
indicates the point corresponding to the onset of the inspiratory effort (Pdi swing). The
second vertical line indicates the point corresponding to the start of
the inspiratory flow. The
dotted horizontal line represents zero flow. in inspiratory flow; ex
expiratory flow. (A) Tidal volume 0.46 L. Note that expiratory flow
ends abruptly before inspiration, whereas the Pdi and Ppl swings have
already begun and Pga has remained constant during that interval. In
this case PEEPi,dyn was measured as the negative deflection in Ppl between the point corresponding to the onset of the Pdi swing and the
point of zero flow. (B) Tidal volume 0.33 L. Note that Pga increases
throughout most of the expiration. By contrast, Pga becomes less positive from the onset of the inspiratory effort indicated by the start of
positive Pdi swing to the start of inspiratory flow. In this case PEEPi,dyn
was measured as the negative Ppl deflection between the point corresponding to the onset of the Pdi swing and the point of zero flow subtracted by the amount of Pga negative deflection observed in that interval. Reprinted by permission from Reference 94.
coworkers (49, 50) and Ward and coworkers (53), the patients
WOB can be estimated noninvasively by comparing the pressurevolume (or pressuretime) relationship with that during
CMV. Differences in WOB among patients, even in the same
patient under different circumstances, may be used to compare the effects of the ventilatory settings, particularly volume
and flow, the internal diameter of the endotracheal tube, the
ventilator devices, or for evaluation of a patients response to
therapy, such as bronchodilators (93, 130132). During assisted modes of ventilation, a patients WOB can be measured
with the esophageal balloon-catheter technique using the
Campbell diagram (Figure 5), which also allows partitioning
between elastic and resistive work, and the detection of expiratory muscle activity. The presence of a positive alveolar
pressure at end-expiration (i.e., intrinsic PEEPi) can considerably increase the area enclosed in the loop and involve supplemental elastic work. Measurement of WOB may help in deciding an appropriate level or type of ventilator assistance and
avoid both excessive and insufficient support. For instance,
continuous flow systems seem to offer less resistance to
breathing than demand flow (i.e., pressure-triggered) systems
and can decrease a patients WOB (86, 93, 133135) (see ASSESSMENT OF THE FUNCTION OF THE ACTIVE CHEST WALL: CAMPBELL DIAGRAM in Section 6 of this Statement).
There is little doubt that measurement of WOB could be
useful in many clinical conditions in ventilator-dependent patients. Automatic systems for its measurement are now available (99, 136138). However, the superiority of the measurement of WOB, over more simple monitoring, for example
over P0.1 (56, 74) or breathing pattern (13), has not been
proved (76). The esophageal balloon technique is unlikely to
616
Transdiaphragmatic pressure can be measured in ICU patients for research or diagnostic purposes when diaphragmatic
dysfunction is suspected. It requires simultaneous recordings
of Pes and Pga; Pdi is obtained by measuring the differential
pressure between these two signals. Because Pga usually rises,
or is positive, during inspiration whereas the Pes signal is usually negative, subtraction of Pes from Pga is, in effect, the sum
of the two tidal excursions. This measurement is described in
more detail elsewhere. The potential applications of this measurement in ICU patients are summarized in subsequent text
(see TECHNIQUES FOR PRESSURE MEASUREMENTS in Section 2 of
this Statement).
Absolute values of the Pdi swings. Although this measurement has not been used for quantification of respiratory muscle dysfunction, its relation to the amplitude of VT is a reflection of the degree of mechanical coupling between the respiratory
muscles and the respiratory system. While a normal subject
may require a Pdi swing of 5 cm H2O to obtain a VT of 500 ml,
a severely diseased patient, as often seen in the ICU, may develop up to 30 cm H2O to achieve only half of this volume
(85). The same reasoning can be used for Pes swings. Minimizing tidal Pdi has also been proposed to be a target for titration
of pressure support ventilation (139).
Maximum Pdi (Pdi,max) and mean Pdi over Pdi,max. This
ratio has been proposed in the laboratory setting to predict
the risk of respiratory muscle fatigue (140). Although it is of
potential interest in the field of intensive care medicine, its use
is limited by the extreme difficulty of obtaining reliable measurements of Pdi,max in this setting (141). It is necessary to
motivate the patient and, in particular, to display the pressure
traces while the patient performs the maneuver. The same
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2002
In mechanically ventilated patients, direct recording of the electrical activity of the crural diaphragm via an esophageal electrode has been used to quantify the activity of this muscle, and
to examine the precise timing of activation (54, 55, 158161)
(see RECORDING ELECTRODES in Section 3 of this Statement).
PREDICTION OF WEANING
617
suffer severe cardiopulmonary or psychological decompensation, which sets the patient back in his or her clinical course.
Although careful clinical assessment is necessary in deciding
when to discontinue mechanical ventilation, this alone is not
sufficient, as demonstrated by Stroetz and Hubmayr (163).
They studied 31 patients being weaned by gradual reductions
in the level of pressure support. The physician in charge of
each patient was asked to predict a patients ability to sustain
unassisted breathing without distress for 1 hour. Of 22 patients
whom the physicians thought likely to fail a weaning trial, 11
were successfully weaned; of nine patients thought likely to be
successfully weaned, three failed the trial. This study provides
clear evidence of the need to employ objective tests, i.e., predictive indices, when deciding if a patient can tolerate the discontinuation of mechanical ventilation.
Several tests have been described to guide the timing and
pace of the weaning process. Because an imbalance between
respiratory mechanical load and respiratory muscle capability
appears to be the major cause of weaning failure (18, 19),
many of the weaning indices directly or indirectly relate to respiratory muscle function. Before assessing respiratory muscle
function in a ventilator-supported patient, it is imperative to
show that the patient is not likely to develop hazardous hypoxemia. Weaning should not be contemplated in a patient
with a PaO2 of less than 55 mm Hg at an inspired oxygen fraction (FIO2 ) of 0.40 or higher, because weaning failure is very
likely in such patients. However, many patients with satisfactory oxygenation fail weaning attempts, and, except in the patient with marked hypoxemia, indices of oxygenation, such as
the PaO2 /FIO2 ratio, are unreliable predictors of weaning outcome (164, 165).
Maximum inspiratory pressure, a measurement of inspiratory muscle strength (see VOLITIONAL TESTS OF RESPIRATORY
MUSCLE STRENGTH in Section 2 of this Statement), is a standard
weaning index. In an early study, Sahn and Lakshminarayan
(61) found that all patients with a PI,max value more negative
than 30 cm H2O were successfully weaned while all patients
with a PI,max less negative than 20 cm H2O failed a weaning
trial. Subsequent investigators have not found PI,max to provide such clear separation between weaning success and weaning failure patients (13, 18, 106, 164169). Studies with accessible data on the accuracy of PI,max are summarized in Table 1.
Because the studies differ in design (prospective, retrospective), method of performing PI,max (best of three attempts,
sustained occlusion for 20 seconds), method of weaning (trials
of spontaneous breathing, intermittent mandatory ventilation,
pressure support), and definitions of weaning success and failure, it is not surprising that accuracy of PI,max varied considerably among the studies. Nevertheless, it is possible to arrive
at some general conclusions. Sensitivity was approximately
0.80, meaning that approximately 80% of patients who succeeded in a weaning trial had a PI,max value that predicted
success (i.e., more negative than 30 cm H2O). However,
specificity was approximately 0.25, meaning that only a minority (25%) of patients who failed a weaning trial had a PI,max
that predicted weaning failure (i.e., less negative than 30 cm
H2O). Moreover, the ability to predict outcome was not improved by employing a standardized method of measuring
PI,max (18, 106, 165). Based on these data, PI,max measurements appear to be more helpful in understanding the reason
why a particular patient failed a weaning trial rather than in
deciding whether to attempt a weaning trial (see additional
discussion of PI,max in this section).
A minute ventilation of less than 10 L/minute, indicating
acceptable ventilatory requirements, is another standard weaning index (61). However, in most studies, minute ventilation
618
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Chatila and coworkers (169) measured fR/VT with a handheld spirometer in 100 medical-cardiac patients being weaned
from mechanical ventilation. The fR/VT ratio was measured
during the first minute of spontaneous breathing, and the patients were then weaned using T-tube trials, CPAP, or pressure-support ventilation. After 3060 minutes, the fR/VT ratio
was again measured. The area under the ROC curve was
higher for the fR/VT ratio measured at 3060 minutes than
during the first minute of spontaneous breathing, 0.92 0.03
and 0.74 0.05, respectively. Interestingly, the area under the
ROC curve for 3060 minutes is similar to that reported by
Yang and Tobin (0.89) (165). This study by Chatila and coworkers (169) emphasizes the importance of not measuring
the fR/VT ratio during the first minute of spontaneous breathing, when respiratory drive may still be suppressed. It does not
necessarily mean that one needs to wait 3060 minutes to
reach a steady-state value that truly represents the patients
clinical status.
In a study of 218 extubated patients in a medical ICU, Epstein and Ciubotaru (173) showed that women have a higher
fR/VT ratio than men, which could not be explained by body
size, and that fR/VT was further increased in women with a
narrow endotracheal tube. Consequently, the false-negative
rate for fR/VT in women with a narrow endotracheal tube ( 7
mm internal diameter) was especially high. When comparing
data from different studies of weaning indices, the pretest
probability of a successful outcome becomes very important.
Epstein and Ciubotaru (173) deliberately selected patients with
a very high pretest probability of successful outcome (0.84),
because every patient tolerated a weaning trial and was extubated; in contrast, outcome was in considerable doubt (pretest
probability 0.56) in the patients studied by Yang and Tobin
(165), who were trying to identify the earliest point in time
that a patient could resume spontaneous ventilation. For identical false-negative (0.03) and true-negative rates (0.64) (166),
the posttest probability of a successful outcome for fR/VT
100 breaths/minute/L, calculated on the basis of Bayes theorem, is 20% for the patients of Epstein and Ciubotaru (173)
versus 5% for the patients of Yang and Tobin (165). In other
words, fR/VT is less helpful in cases when the physician
strongly suspects that the patient can tolerate weaning and extubation than when the physician is very doubtful about a patients outcome.
Recently, Ely and coworkers (129) investigated whether
the combination of predictive indices followed by a trial of
spontaneous breathing would hasten the pace of weaning.
Over a 9-month period, ventilator-supported patients in their
medical ICU and coronary care units were screened each
morning for five factors: PaO2/FIO2 ratio
200; PEEP 5 cm
H2O; fR/VT 105 breaths/minute/L; intact cough on suctioning; and absence of infusions of sedative or vasopressor agents.
Sensitivity
Specificity
Reference Number
0.68
1.00
NA
NA
1.00
1.00
0.86
0.91
0.90
0.67
0
0
NA
NA
0.11
0.14
0.21
0.30
0.26
0.69
0.56
0.67
0.91
0.92
0.59
0.60
0.58
0.82
0.67
0.78
0
0
0.22
0.21
1.00
1.00
0.55
0.55
0.60
0.55
166
167
164
164
165
165
165
168
169
169
619
Figure 7. Receiver operating characteristic (ROC) curves for frequency/tidal volume (f/VT) ratio, CROP index (an index that integrates measurements of dynamic compliance, respiratory rate, arterial oxygenation, and maximal inspiratory pressure),
maximal
inspiratory pressure (PI,max), and minute ventilation ( VE) in 36 patients who were successfully weaned and 28 patients who failed a
weaning trial. The ROC curve is generated by plotting the proportion of true positive results against the proportion of false positive results for each value of a test. The curve for an arbitrary test that is expected a priori to have no discriminatory value appears as a diagonal
line, whereas a useful test has an ROC curve that rises rapidly and
reaches a plateau. The area under the curve (shaded) is expressed
(boxed) as a proportion of the total area. Reprinted by permission
from Reference 165.
CONCLUSION
This Section of the Statement has reviewed the tests of respiratory muscle function, direct and indirect, that are relevant to
the particular environment of the ICU. The scientific basis
and methodology of many of these tests are discussed in earlier Sections of the Statement. This article also focuses on the
crucial issue of weaning from mechanical ventilation.
Abnormalities of the pattern of breathing are common in
ICU patients, especially in those with respiratory muscle dysfunction. Tachypnea is a sensitive marker of deteriorating
clinical status, but is not specific. Paradoxical motion of the rib
cage and abdomen occurs with elevated respiratory load, but
is not diagnostic of respiratory muscle fatigue. Measurements
of maximum inspiratory pressure have poor reproducibility in
critically ill patients and are of limited use for decision making
in the ICU. Airway occlusion pressure (P0.1) is easy to measure in patients receiving assisted ventilation, and high values
signal increased respiratory motor output. The most direct
measures of patient effort are work of breathing and PTP, but
these measurements require considerable attention to detail
and their use is confined to research settings. A scooped contour of the airway pressure tracing during volume and flow
preset assisted ventilation indicates patient effort. The relative
Likelihood Ratio
80
80100
100
Definition of abbreviations: fR respiratory frequency; VT tidal volume.
* Based on data of Yang and Tobin (171).
7.53
0.77
0.04
620
20.
21.
22.
23.
24.
25.
26.
27.
28.
29.
30.
31.
32.
33.
34.
35.
36.
37.
38.
39.
40.
41.
42.
43.
44.
45.
46.
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2002
621
72. Sassoon CSH, Te TT, Mahutte CK, Light RW. Airway occlusion pressure: an important indicator for successful weaning in patients with
chronic obstructive pulmonary disease. Am Rev Respir Dis 1987;
135:107113.
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THIS OFFICIAL STATEMENT WAS PREPARED BY AN AD-HOC SUBCOMMITTEE OF THE ASSEMBLY ON RESPIRATORY STRUCTURE AND
FUNCTION. THE SUBCOMMITTEE WAS CHAIRED BY ALEX GRASSINO (ATS CO-CHAIR) AND JOHN MOXHAM (ERS CO-CHAIR).
MEMBERS OF THE SUBCOMMITTEE ARE:
Alex E. Grassino, ATS Co-Chair, Centre Hospitalier de
lUniversit de Montreal and Meakins-Christie Laboratories, McGill University, Montreal, Quebec, Canada
John Moxham, ERS Co-Chair, Department of Respiratory
Medicine, Kings College Hospital, London, United Kingdom
THOMAS K. ALDRICH, Pulmonary Section, Department of
Medicine, Montefiore Medical Center and Albert Einstein College of Medicine, Bronx, New York
JULIAN ALLEN, Childrens Hospital of Philadelphia, Philadelphia, Pennsylvania
FRANOIS BELLEMARE, Department of Anesthesia, Centre
Hospitalier de lUniversit de Montreal, Montreal, Quebec, Canada
LAURENT BROCHARD, Hpital Henri Mondor, Creteil, France
PETER M. CALVERLY, Fazakerly Hospital, Liverpool, England
BARTOLOME R. CELLI, Pulmonary Critical Care, St. Elizabeths
Medical Center, Boston, Massachusetts
THOMAS CLANTON, Pulmonary Division, Ohio State University, Columbus, Ohio
NEIL J. DOUGLAS, Respiratory Medicine Unit, Department
of Medicine, Royal Infirmary, Edinburgh, United Kingdom
SANDRA ENGLAND, University of Medicine and Dentistry of
New Jersey-Robert Wood Johnson Medical School, New
Brunswick, New Jersey
MARC ESTENNE, Department of Chest Medicine, Erasme
University Hospital, Universit Libre de Bruxelles, Brussels, Belgium
JEAN WILL FITTING, Division de Pneumologie, Centre Hospitalier de lUniversit Vaudois, Lausanne, Switzerland
SIMON C. GANDEVIA, Prince of Wales Medical Research Institute, Sydney, Australia
CLAUDE GAULTIER, Department of Physiology, Hpital
Robert-Debre, Paris, France
G. JOHN GIBSON, Freeman Hospital, Newcastle upon Tyne,
United Kingdom